Displaying One Session
- Natasha Leighl (Toronto, Canada)
- Suresh Senan (Amsterdam, Netherlands)
- Alona Zer (Petah Tikva, Israel)
LBA56 - ORIENT-12: Sintilimab plus gemcitabine and platinum (GP) as first-line (1L) treatment for locally advanced or metastatic squamous non-small-cell lung cancer (sqNSCLC)
- Caicun Zhou (Shanghai, China)
Abstract
Background
Sintilimab, an anti-PD-1 antibody, plus GP showed promising efficacy and acceptable safety in 1L sqNSCLC in a phase Ib study. ORIENT-12, a randomized, double-blind, phase III study, compared the efficacy and safety of sintilimab plus GP with placebo plus GP as 1L treatment for patients with locally advanced or metastatic sqNSCLC (NCT03629925).
Methods
Patients with histologically/cytologically confirmed stage IIIB/C (ineligible for concurrent chemoradiation or surgery) and stage IV sqNSCLC were enrolled and randomized 1:1 to receive either sintilimab (S group) or placebo (P group) with GP every 3 weeks for 4 or 6 cycles, followed by sintilimab or placebo as maintenance therapy. Stratification factors included disease stage (IIIB/C vs IV), platinum (cisplatin vs. carboplatin), PD-L1 expression (TPS, ≥1% vs <1%). Conditional crossover was allowed. The primary endpoint was progression-free survival (PFS) assessed by Independent Radiographic Review Committee (IRRC) per RECIST v1.1.
Results
A total of 357 pts were enrolled and randomized to S group (n=179) and P group (n=178). At interim analysis (median follow-up 8.0 mon), mPFS (by IRRC) was 5.1 mo in S group vs 4.9 mo in P group (HR, 0.621; 95% CI 0.473 - 0.815; P=0.00056). mPFS benefit was also observed by investigator assessment (5.9 mo vs. 4.9 mo, HR, 0.575; 95%CI 0.435 - 0.761; P=0.00009). The mOS was not reached in both groups, but showed a nominally significant improvement favoring S group (HR, 0.567, 95%CI, 0.353 to 0.909, P=0.01701). The PFS benefit with sintilimab plus GP was observed in all PD-L1 subgroups. The incidence of grade ≥3 adverse events was similar between groups (86.6% vs 83.1%). No new safety signals were observed.
Conclusions
ORIENT-12 is the first study globally to demonstrate superiority of an anti-PD-1 antibody plus GP over GP in PFS and OS with acceptable safety profile as 1L treatment for locally advanced or metastatic sqNSCLC.
Clinical trial identification
NCT03629925.
Legal entity responsible for the study
Innovent Biologics, Inc.
Funding
Innovent Biologics, Inc. and Eli Lilly and Company.
Disclosure
W. Zhang, W. Yang, S. Wang, H. Zhou: Full/Part-time employment: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.
LBA57 - MHC-II antigen presentation pathway as a predictive biomarker for sintilimab plus chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC)
- Yunpeng Yang (Guangzhou, China)
Abstract
Background
Immunotherapy plus chemotherapy is a promising treatment for first-line nsq-NSCLC. However, predictive biomarkers for this immuno-combination remain to be elucidated.
Methods
In a randomized, double-blind, phase III study evaluating the efficacy of sintilimab, an anti-PD-1 antibody, plus pemetrexed and platinum (Chemo) as first-line treatment (ORIENT-11), 397 patients with locally advanced or metastatic nsq-NSCLC were randomized (2:1 ratio) to receive either sintilimab plus Chemo (Combo) or placebo plus Chemo. The primary endpoint was progression-free survival (PFS). RNA sequencing was conducted on 248 baseline tumor biopsies (168 in Combo and 80 in Chemo).
Results
Combo group showed superiority to Chemo group in PFS (HR=0.48, 95%CI: 0.36-0.64, p<0.0001). Survival analysis showed that top 20 genes (Ranked by P-value) including ITGB2, ADAP2, MPP1, PIK3AP1, GBGT1, RAB27A, CD180, NEK6, RLN3, CD84, CASP8, DRAM1, HLA-DMB, OTULIN, HELZ, VDR, HLA-DPA1, MX2, FUCA1, MKRN1 were significantly associated with good efficacy of Combo treatment (mean HR 0.26, P<0.0001) but not Chemo treatment except for NEK6 (HR, 0.38; 95% CI, 0.14−0.50; P=0.0047). In line with this, we found that the entire signature score of MHC-II antigen presentation pathway was more significantly associated with clinical efficacy of Combo (HR, 0.51; 95% CI, 0.28-0.91; P=0.0230) than that of MHC-I (HR, 0.70; 95% CI, 0.39−1.25; P=0.2230). It was further validated that cells with MHC-II presentation capability also contributed to the longer PFS in the Combo group, e.g. macrophage (HR, 0.48; P=0.0120), activated dendritic cell (HR, 0.46; P=0.0114), immature dendritic cell (HR, 0.47; P=0.0134), or immature B cell (HR, 0.51; P=0.0245). Finally, multiplex immunohistochemistry data from 57 patients demonstrated concordance between RNA and protein expression and that higher level of CD68 protein was associated with good outcome (HR, 0.42; 95% CI, 0.12-1.54; P=0.1930).
Conclusions
Signature of MHC-II antigen presentation was significantly associated with longer PFS in patients receiving immune-combination therapy and could be served as a predictive biomarker.
Clinical trial identification
NCT03607539.
Legal entity responsible for the study
Innovent Biologics, Inc.
Funding
Innovent Biologics Inc. and Eli Lilly and Company.
Disclosure
J. Sun, H. Zhou, S. Wang, W. Xu, B. Peng: Full/Part-time employment: Innovent Biologics Inc. L. Zhang: Research grant/Funding (self): Eli Lilly and Company; Research grant/Funding (self): Pfizer. All other authors have declared no conflicts of interest.
1260MO - Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): Step 1 results of phase III ATALANTE-1 randomised trial
- Giuseppe Giaccone (New York, AL, United States of America)
Abstract
Background
Tedopi® is an anticancer vaccine with modified neoepitopes restricted to HLA-A2+ targeting five tumor-associated antigens frequently expressed in lung cancer: CEA, HER2, MAGE2, MAGE3 and P53. ATALANTE-1 was a randomized, open-label, 2-Step phase 3 study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on ICI.
Methods
HLA-A2+ NSCLC patients,
Results
At cutoff of February 2020, 99 patients (Tedopi® n=63; SoC n=36) were randomized and analyzable for Step-1. The 1y-OS was 29/63 (46%) [95%CI 33-59]) in Tedopi® group and 13/36 (36%) [95%CI 21-54] in SoC. The Step-1 endpoint has shown a lower limit of the 95% confidence interval above the futility boundary (25%) with an OS estimate of 10% above the estimate of SoC. Secondary endpoints and subgroup data will be further presented. Grade 3-4 related TEAEs were 11 % in Tedopi® group and 43 % in SoC. There was no related grade 5 TEAE. Related TEAE leading to withdrawal from the study were also less frequent in Tedopi® group (6%) versus SoC (14%). Due to the risk of COVID-19 pandemic on data integrity, following recommendation of the Independent Data Monitoring Committee and Steering Committee, the decision was taken to early terminate the study at Step-1 and definitely stop new accrual while continuing the OS follow-up in all patients.
Conclusions
The Step-1 primary endpoint was positively achieved with a 1y-OS rate of 46% and a good safety profile. Step-1 results shown a favorable benefit/risk of Tedopi® over SoC as 2nd or 3rd line treatment in advanced HLA-A2+ NSCLC patients after failure to ICI.
Clinical trial identification
EudraCT: 2015-003183-36; NCT02654587.
Legal entity responsible for the study
OSE Immunotherapeutics.
Funding
OSE Immunotherapeutics.
Disclosure
G. Giaccone: Advisory/Consultancy: CStone; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi; Research grant/Funding (institution): Medimunne; Research grant/Funding (institution): Incyte. E. Felip: Advisory/Consultancy: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Blueprint Medicine; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Elli Lilly; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck KgaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy: GSK; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Medscape; Speaker Bureau/Expert testimony: Prime Oncology; Speaker Bureau/Expert testimony: Touchime ; Research grant/Funding (institution): Fundation Merck Salud; Advisory/Consultancy: Grifols. R. Garcia Campelo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. F. DENIS: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Shugai; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: MSD; Advisory/Consultancy, Licensing/Royalties: Sivan. E. Quoix: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: Shugai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Takeda; Honoraria (self), interview at ASCO 2019: Medscape. A. Madroszyk: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: MSD. D. Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self): Shugai; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Sandoz; Travel/Accommodation/Expenses: Boehringer Ingelheim. W. Hilgers: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self): MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche. T. Moran: Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer Ingelheim. D. Galetta: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca. F. Cappuzzo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. G. Robinet: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZenaca; Advisory/Consultancy: BMS. S. Viteri: Full/Part-time employment: Pangaea Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (self), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution), Travel/Accommodation/Expenses: Ose Immunotherapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KgaA; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Boston Pharmaceuticals; Research grant/Funding (institution): Exelexis; Research grant/Funding (institution): Novocure; Research grant/Funding (institution): MedImmune. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardian 360; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genesort; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck KgaA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NovellusDx; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. D. Costantini: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: OSE Immunotherapeutics. R. Dziadziuszko: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Foundation Medicine; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy: Seattle Genetics. B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Blueprint Medicine; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Cellgene; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daichi-Sankyo; Research grant/Funding (institution): Elli-Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KgaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): Ose Immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.
Invited Discussant LBA56, LBA57 and 1260MO
LBA58 - ORR in patients receiving nivolumab plus radiotherapy in advanced non-small cell lung cancer: First results from the FORCE trial
- Farastuk Bozorgmehr (Heidelberg, Germany)
Abstract
Background
The FORCE trial addressed the hypothesis that applying radiation together with anti-PD-1 immunotherapies may foster immune response, by combining nivolumab and radiation in non-small cell lung cancer (NSCLC) patients with clinical indication for radiotherapy.
Methods
From 02/17-12/19, 101 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment were enrolled in this multicentre, prospective, non-randomized phase II trial. 41 patients with a clinical indication for palliative radiotherapy received nivolumab 240 mg followed by 5 x 4 Gy on consecutive days to metastasis (53% bone, 18% lymph node, 29% other), initiated 72 hours after first nivolumab administration (Group A). 60 patients without an indication for radiotherapy received nivolumab only (Group B). Nivolumab was administered every two weeks in both groups and continued until progression or limiting toxicities. In both groups, biomaterials were collected systematically for exploratory hypothesis-generating analyses.
Results
Whilst some patient baseline characteristics, e.g. age, gender, smoking status and number of previous therapies were similar in both groups, preliminary analyses indicate an imbalance with a number of unfavourable characteristics being more prevalent in group A (e.g. ECOG 1, 81% vs 58%; extrathoracic metastases, 93% vs. 63%; p<0.05). Treatment related grade 3-4 adverse events occurred at similar rates in both groups (17% vs. 15%, p=0.8). The primary objective was to achieve an objective response rate (ORR) of > 19% per RECIST criteria 1.1 in group A. With an ORR of 8.3% in group A, this target was not met (p=0.991 for one-sided binomial test). ORR in group B was 23.8%. Patients with missing tumor response assessment due to tumor-related death (group A and B: 8 and 5) were considered non-responders.
Conclusions
The combination of nivolumab and palliative radiotherapy was safe and feasible; however, it did not improve ORR in the setting of this exploration. The requirement for a clinical indication for palliative radiotherapy enforced selection of patients with unfavourable properties into group A. Clinical characteristics need consideration when assessing the efficacy of immunotherapy.
Clinical trial identification
EudraCT Nr.: 2015-005741-3; NCT03044626.
Legal entity responsible for the study
AIO-Studien gGmbH.
Funding
Bristol Myers Squibb.
Disclosure
F. Bozorgmehr: Research grant/Funding (self): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Chugai. A. Atmaca: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca. M. Faehling: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. N. Reinmuth: Honoraria (self), Advisory/Consultancy: BMS. A. Stenzinger: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Illumina; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: ThermoFischer; Research grant/Funding (institution): Chugai. M. Thomas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Chugai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. All other authors have declared no conflicts of interest.
LBA59 - First-line nivolumab (NIVO) + ipilimumab (IPI) combined with 2 cycles of platinum-based chemotherapy (chemo) vs 4 cycles of chemo in advanced non-small cell lung cancer (NSCLC): Patient-reported outcomes (PROs) from CheckMate 9LA
- Martin Reck (Grosshansdorf, Germany)
Abstract
Background
CheckMate 9LA (NCT03215706), a phase III randomized study, met its primary endpoint of improved overall survival with NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of chemo (n = 361) vs 4 cycles of chemo (n = 358) in patients (pts) with treatment-naive, stage IV/recurrent NSCLC and no known sensitizing
Methods
PROs were exploratory endpoints; disease-related symptoms were evaluated using the Lung Cancer Symptom Scale average symptom burden index and 3-item global index (LCSS ASBI/3-IGI); health-related quality of life (HRQoL) was evaluated using EQ-5D-3L visual analog scale and utility index (EQ-5D-3L VAS/UI). Analyses included mean changes from baseline, mixed-effect model repeated measures (MMRM) of longitudinal changes, and time to deterioration.
Results
PRO completion rates were > 80% across arms for most on-treatment assessment time points in which there were ≥ 10 pts (up to week 90 for NIVO + IPI + chemo and week 78 for chemo). A trend for improvement in LCSS ASBI and 3-IGI was seen in both treatment arms, though the minimally important difference was not reached. In both arms, mean EQ-5D-3L VAS scores approached UK population norms after ∼30 weeks. MMRM analyses showed similar improvement across arms in overall LCSS ASBI when there was a sufficient number of patients in both study arms for assessment (up to week 78). There was a decreased risk of, and delayed time to, definitive deterioration with NIVO + IPI + chemo vs chemo (Table).
Conclusions
Pts with advanced NSCLC treated with NIVO + IPI + chemo (2 cycles) maintained their quality of life as compared with chemo (4 cycles). Pts in the NIVO + IPI + chemo arm had decreased risk of definitive deterioration in HRQoL and symptoms vs chemo. Time to deterioration with NIVO + IPI + chemo (2 cycles) vs chemo (4 cycles) Includes on-treatment and follow-up. aHR < 1 favors NIVO + IPI + chemo over chemo. bTime from randomization to when change in PRO score first meets/exceeds deterioration threshold. cIn addition to initial assessment, all subsequent assessments must meet/exceed the threshold. dBased on UK norms.
HRa (95% CI) Time to first deteriorationb LCSS ASBI 1.16 (0.91–1.48) LCSS 3-IGI 1.10 (0.89–1.36) EQ-5D-3L VAS 1.07 (0.88–1.30) EQ-5D-3L UId 0.88 (0.72–1.07) LCSS ASBI 0.66 (0.47–0.92) LCSS 3-IGI 0.66 (0.50–0.88) EQ-5D-3L VAS 0.73 (0.58–0.93) EQ-5D-3L UId 0.72 (0.57–0.90)
Clinical trial identification
NCT03215706.
Editorial acknowledgement
Professional writing assistance was provided by Laura Yee, of Caudex, funded by Bristol-Myers Squibb Company.
Legal entity responsible for the study
Bristol-Myers Squibb Company.
Funding
Bristol-Myers Squibb Company.
Disclosure
M. Reck: Advisory/Consultancy, Travel/Accommodation/Expenses: Abbvie; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer-Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Samsung. T-E. Ciuleanu: Advisory/Consultancy, Travel/Accommodation/Expenses: Astella Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: AD Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. M. Schenker: Research grant/Funding (self, related to the current clinical trial), Research grant/Funding (institution, related to the current clinical trial): Bristol Myers Squibb; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): MSD; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): AstraZeneca; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Pfizer; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Regeneron; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Novartis; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Roche; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Astellas; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): AbbVie; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Bayer; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Eli Lilly; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Merck Serono; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Gilead; Research grant/Funding (self, not related to the current clinical trial), Research grant/Funding (institution, not related to the current clinical trial): Amgen. B. Zurawski: Honoraria (self), Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Speaker Bureau/Expert testimony: Astellas; Honoraria (self), Speaker Bureau/Expert testimony: MSD; Honoraria (self), Speaker Bureau/Expert testimony: Bristol Myers Squibb; Honoraria (self): Janssen Cilag; Honoraria (self): AstraZeneca. J. Bennouna: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: Bayer. L. Paz-Ares: Honoraria: Adacap; Honoraria: Amgen; Honoraria, Research grant/Funding: AstraZeneca; Honoraria: Bayer; Honoraria, Blueprint Medicines; Honoraria, Boehringer Ingelheim; Honoraria, Research grant/Funding: Bristol Myers Squibb; Honoraria: Celgene; Honoraria: Eli Lilly; Honoraria: Incyte; Honoraria: Ipsen; Honoraria, Research grant/Funding: Merck Sharp and Dohme; Honoraria: Novartis; Honoraria, Research grant/Funding: Pfizer; Honoraria: PharmaMar; Honoraria: Roche; Honoraria: Sanofi; Honoraria: Servier; Honoraria: Sysmex; Honoraria: Takeka; Leadership role: Altum sequencing; Officer/Board of Directors: Genómica. S. Lu: Advisory/Consultancy, Speaker bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Heng Rui; Advisory/Consultancy, Research grant/Funding (self): Hutchison Medipharma; Advisory/Consultancy: Simcere; Advisory/Consultancy: ZaiLab; Advisory/Consultancy: GenomiCare; Advisory/Consultancy, Speaker bureau/Expert testimony, Research grant/Funding (self): Roche; Speaker bureau/Expert testimony: Hansoh. T. John: Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bayer; Advisory/Consultancy: Takeda; Honoraria (institution): Specialised Therapeutics; Honoraria (institution): Pfizer; Honoraria (institution): Novartis. B. Padilla, X. Sun, A. Moisei: Full-time employment: Adelphi Values. J. Yan, Y. Yuan: Full-time employment: Bristol Myers Squibb. S.I. Blum: Full-time employment, Stockholder: Bristol Myers Squibb. D.P. Carbone: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/ Expenses: AstraZeneca; Honoraria (self): Nexus Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/ Consultancy, Travel/Accommodation/Expenses: AbbVie; Leadership role: The Ohio State University; Leadership role: ASCO and AACR; Leadership role: NCI; Leadership role: Eastern Cooperative Oncology Group and the Thoracic Core committees for both the Alliance and ECOG/ACRIN; Leadership role, Past president: International Association for the Study of Lung Cancer (IASLC); Leadership role: Damon Runyon, K08, ASCO, AACR, CDA, LIFE and IDEA; Leadership role, Leader: Vanderbilt CCC’s Host-Tumor Interactions and Thoracic/Head and Neck Programs; Leadership role: Vanderbilt Lung Cancer SPORE, and an NCI U01 consortium; Officer/ Board of Directors: IASLC, LCFA, LUNGevity, ALCMI, Joan’s Legacy Foundation, Lance Armstrong Foundation, Wendy Wyrick Foundation, Wendy Will Case Foundation, Jack Roth Foundation; Full/ Part-time employment, Professor of Medicine: The Ohio State University Comprehensive Cancer Center; Advisory/Consultancy, Travel/Accommodation/Expenses: EMD Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Inviata; Advisory/Consultancy, Travel/Accommodation/Expenses: Inovio; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Loxo Oncology; Advisory/Consultancy, Travel/Accommodation/ Expenses: Merck, Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/ Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/ Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda Oncology; Advisory/ Consultancy, Travel/Accommodation/Expenses: Trinity; Advisory/Consultancy, Travel/Accommodation/ Expenses: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Kyowa Kirin; Advisory/ Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/ Accommodation/Expenses: Gritstone Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche China; Advisory/Consultancy, Travel/Accommodation/Expenses: GenePlus; Advisory/Consultancy, Travel/ Accommodation/Expenses: Daiichi Sankyo Inc; Advisory/Consultancy: Seattle Genetics, GI Therapeutics (Intellisphere), Gloria Biosciences. All other authors have declared no conflicts of interest.
Invited Discussant LBA58 and LBA59
LBA60 - ZENITH20, a multinational, multi-cohort phase II study of poziotinib in NSCLC patients with EGFR or HER2 exon 20 insertion mutations
- Mark A. Socinski (Orlando, PA, United States of America)
Abstract
Background
Treatment of non-small cell lung cancer (NSCLC) with EGFR or HER2 exon 20 mutations is a serious unmet medical need. We are evaluating the efficacy and safety of poziotinib, a potent EGFR and HER2 exon 20 tyrosine kinase inhibitor (TKI), in a large, prospective multi-cohort study (N=603). Here, we report results from a cohort of previously treated patients with advanced NSCLC exon 20 insertion mutations (ZENITH20-2 N=90).
Methods
Patients enrolled in ZENITH20-2 had HER2 exon 20 insertion mutations per a CLIA certified (or equivalent) sequencing test. Poziotinib (16 mg) was administered orally QD, allowing dose interruptions/reductions for toxicity if needed. The primary endpoint was objective response rate (ORR), evaluated centrally by an independent image review committee using RECIST 1.1 with a 95% CI pre-specified lower bound of 17%. Secondary endpoints included disease control rate, duration of response, progression-free survival, and safety.
Results
In ZENITH20-2
Conclusions
ZENITH20-2 met its ORR primary efficacy endpoint with durable responses and presented a manageable safety profile, typical of 2nd generation TKIs. Additional cohorts are enrolling to explore alternative dose levels and BID dosing.
Clinical trial identification
NCT03318939.
Legal entity responsible for the study
Spectrum Pharmaceuticals.
Funding
Spectrum Pharmaceuticals.
Disclosure
M.A. Socinski: Research grant/Funding (institution): Spectrum Pharmaceuticals. R. Cornelissen: Research grant/Funding (institution): Spectrum Pharmaceuticals. M.C. Garassino: Research grant/Funding (institution): Spectrum Pharmaceuticals. J. Clarke: Research grant/Funding (institution): Spectrum Pharmaceuticals. N. Tchekmedyian: Research grant/Funding (institution): Spectrum Pharmaceuticals. J. Molina: Research grant/Funding (institution): Spectrum Pharmaceuticals. J.W. Goldman: Research grant/Funding (institution): Spectrum Pharmaceuticals. G. Bhat: Full/Part-time employment: Spectrum Pharmaceuticals. F. Lebel: Full/Part-time employment: Spectrum Pharmaceuticals. X. Le: Research grant/Funding (institution): Spectrum Pharmaceuticals.
LBA61 - First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions
- Stephen V. Liu (Washington, United States of America)
Abstract
Background
Tarloxotinib is a hypoxia-activated prodrug of a pan-ErbB kinase inhibitor that releases a potent irreversible active metabolite (tarloxotinib-E) under hypoxic conditions to preferentially deliver the active moiety to tumor versus normal tissues. Tarloxotinib has shown preclinical efficacy in
Methods
Patients (pts) with advanced NSCLC harboring an
Results
As of June 12, 2020, 23 pts (11 cohort A, 11 cohort B, 1 cohort C) were treated with tarloxotinib. The disease control rate for all evaluable pts was 60% (12/20). In cohort A, the best response was stable disease (SD) in 6/11 (55%) and progressive disease (PD) in 5/11 (45%). In cohort B, 4/9 evaluable pts (44%) exhibited tumor reduction by RECIST and 2/9 pts experienced confirmed PR (22%), 4/9 (44%) pts had SD, and 3/9 (33%) pts had PD. Three pts in cohort B were treated beyond 6 months with 3 pts still ongoing. Most treatment emergent adverse events (TEAEs) were grade 1/2. Those occurring at >20% were prolonged QTc (60.9%), rash (43.5%), nausea (21.7%), and diarrhea (21.7%). The grade 3 TEAEs were prolonged QTc (34.8%), rash (4.3%), diarrhea (4.3%) and increased ALT (4.3%). Five of 23 (21.7%) pts required dose reduction and only 1/23 (4.3%) pts discontinued tarloxotinib due to a drug-related adverse event (infusion reaction).
Conclusions
Tarloxotinib exhibits antitumor activity in NSCLC pts with
Clinical trial identification
NCT03805841.
Legal entity responsible for the study
Rain Therapeutics.
Funding
Rain Therapeutics.
Disclosure
S.V. Liu: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Boehringer Ingehleim; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Catalyst; Advisory/Consultancy: Celgene; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Inivata; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck/MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Takeda; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Molecular Partners; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): RAPT; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Turning Point Therapeutics. L.C. Villaruz: Advisory/Consultancy: Achilles; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): GSK. V.H.F. Lee: Honoraria (self): AstraZeneca; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): BMS; Research grant/Funding (self): Merck Sharp & Dohme; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis. V.W. Zhu: Honoraria (self): AstraZeneca; Honoraria (self): Roche-Foundation Medicine; Honoraria (self): Roche / Genentech; Honoraria (self): Takeda; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche / Genentech; Advisory/Consultancy: Takeda; Advisory/Consultancy: TP Therapeutics; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche-Foundation Medicine; Speaker Bureau/Expert testimony: Roche / Genentech; Speaker Bureau/Expert testimony: Takeda; Shareholder/Stockholder/Stock options: TP Therapeutics. C.S. Baik: Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Calgene Inc.; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): SWOG; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): BluePrint Medicines; Research grant/Funding (institution): Daiichi Sankyo Inc; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): TP Therapeutics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly Oncology. A. Sacher: Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Genentech-Roche; Honoraria (self): Kisoli; Honoraria (self): BMS; Honoraria (self): Bayer; Honoraria (self): Tesaro; Honoraria (self): Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Genentech-Roche; Advisory/Consultancy: Kisoli; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer. C.E. McCoach: Honoraria (self): Novartis; Honoraria (self): Guardant health; Advisory/Consultancy: Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Revolution Medicines; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Takeda. D. Nguyen: Full/Part-time employment: Pacific Shores Medical Group. J.Y-C. Li: Advisory/Consultancy: Roche Hong Kong; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Lilly Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Research grant/Funding (self): Roche Hong Kong; Travel/Accommodation/Expenses: Roche Hng Kong; Travel/Accommodation/Expenses: Taiho; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Sanomic & xcelom; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Mundipharma. J.M. Pacheco: Honoraria (self): Takeda; Honoraria (self): Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Gerson Lehrman Group; Advisory/Consultancy: Hengrui Pharmaceuticals; Advisory/Consultancy: Jazz Pharmaceuticals; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda; Research grant/Funding (institution): Pfizer; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Takeda. C. Kim: Advisory/Consultancy: Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Altor Bioscience. T.F. Burns: Advisory/Consultancy: Novartis; Advisory/Consultancy: Blueprint Medicine; Advisory/Consultancy: Thermo Fisher Scientific. E.L. Schenk: Honoraria (self): Medscape; Honoraria (self): Physician’s Education Resource; Advisory/Consultancy: AbbVie; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Roche; Full/Part-time employment: Practice Update. N. Leighl: Honoraria (self): MSD; Honoraria (self): BMS; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Array; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MSD. L. Tozzi: Shareholder/Stockholder/Stock options: Rain Therapeutics; Full/Part-time employment: Rain Therapeutics. D.R. Camidge: Advisory/Consultancy: Anchiarno; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: CBT Pharmaceuticals; Advisory/Consultancy: Achilles; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bio-Thera; Advisory/Consultancy: Blueprint; Advisory/Consultancy: BeyondSpring; Advisory/Consultancy: Apollomics; Advisory/Consultancy: 14ner/Elevation; Advisory/Consultancy: Archer; Advisory/Consultancy: Helssin; Advisory/Consultancy: BMS; Advisory/Consultancy: Lilly; Advisory/Consultancy: Medtronic; Advisory/Consultancy: Ribon; Leadership role: AbbVie; Leadership role: AstraZeneca; Leadership role: BMS; Leadership role: GSK; Leadership role: Hanosh; Leadership role: Inhibrx; Leadership role: Lycera.
1261MO - Updated results from a phase I/II study of mobocertinib (TAK-788) in NSCLC with EGFR exon 20 insertions (exon20ins)
- Gregory J. Riely (New York, NY, United States of America)
Abstract
Background
Methods
Antitumor activity by investigator-assessed radiographic response (RECIST 1.1) and toxicity (NCI CTCAE) were determined for pts with advanced, previously treated NSCLC with
Results
As of 27 Jan 2020, 28 pts with previously treated NSCLC and
Conclusions
Mobocertinib demonstrated antitumor activity in pts with advanced NSCLC with
Clinical trial identification
NCT02716116 Release date: March 23, 2016.
Editorial acknowledgement
Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
G.J. Riely: Travel/Accommodation/Expenses: Merck, Sharp & Dohme; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Infinity Pharmaceuticals; Research grant/Funding (institution): ARIAD; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Merck. J.W. Neal: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy: Lilly; Honoraria (self): Calithera Biosciences; Honoraria (self): Research to Practice; Honoraria (self): MLI Peerview; Honoraria (self): Medscape; Honoraria (self): Biomedical Learning Institute; Honoraria (self): Prime Oncology; Honoraria (self): Rockpointe; Honoraria (self): CME Matters; Honoraria (self): MJH CME; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (self): Nektar; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): GSK. D.R. Camidge: Honoraria (self): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Arrys/Kyn; Honoraria (self): Genoptix; Honoraria (self): GI Therapeutics (DSMB); Honoraria (self): Mersana Therapeutics; Honoraria (self): Roche/Genentech; Honoraria (self): Ignyta; Honoraria (self): Daiichi Sankyo (ILD adjudication committee); Honoraria (self): Hansoh SRC; Honoraria (self): Bio-Thera DSMB; Honoraria (self): Lycera; Honoraria (self): Revolution Med; Honoraria (self): Orion; Honoraria (self): Clovis; Honoraria (self): Celgene; Honoraria (self): Novartis; Research grant/Funding (self): ARIAD/Takeda. A. Spira: Advisory/Consultancy: ARIAD; Honoraria (self): AstraZeneca; Honoraria (self): Clovis Oncology; Honoraria (self), Speaker Bureau/Expert testimony: Roche. Z. Piotrowska: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: ARIAD; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Guardant Health; Advisory/Consultancy, Research grant/Funding (self): Spectrum; Advisory/Consultancy: ImmunoGen. L. Horn: Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Xcovery; Advisory/Consultancy: Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Incyte; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Boehringer Ingelheim. D.B. Costa: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda/Millennium Pharmaceuticals; Honoraria (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Spectrum. A. Tsao: Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): MedImmune; Advisory/Consultancy: Imedex; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Advisory/Consultancy: Epizyme; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: ARIAD; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Takeda; Advisory/Consultancy: HERON; Licensing/Royalties: UptoDate; Research grant/Funding (self): Seattle Genetics; Research grant/Funding (self): Millennium; Research grant/Funding (self): Polaris; Research grant/Funding (institution): Merck. J. Patel: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda. S. Gadgeel: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: ARIAD; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: AbbVie; Research grant/Funding (institution), Travel/Accommodation/Expenses: ARIAD/Takeda; Research grant/Funding (self), Research grant/Funding (institution): Merck; Research grant/Funding (institution): Blueprint Medicines. L. Bazhenova: Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (self): BeyondSpring Pharmaceuticals; Advisory/Consultancy: GI Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BI; Advisory/Consultancy: Takeda; Advisory/Consultancy: Blueprint; Shareholder/Stockholder/Stock options: Epic Sciences. V.W. Zhu: Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Roche-Foundation Medicine; Honoraria (self), Speaker Bureau/Expert testimony: Roche/Genentech; Honoraria (self), Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Shareholder/Stockholder/Stock options: TP Therapeutics. H. West: Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech/Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda/ARIAD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. R. Gentzler: Honoraria (self): Rockpointe CME; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Jounce; Research grant/Funding (institution): Helsinn. V. Bunn: Full/Part-time employment: Takeda. S. Jin: Full/Part-time employment: Takeda. Z. Feng: Full/Part-time employment: Takeda. P.A. Jänne: Advisory/Consultancy: Araxes Pharmaceuticals; Advisory/Consultancy: ARIAD/Takeda; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Ignyta; Advisory/Consultancy, Research grant/Funding (self): Lilly; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Loxo Oncology; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Voronoi; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Advisory/Consultancy: SFJ Pharmaceuticals; Advisory/Consultancy: Biocartis; Research grant/Funding (self): Astellas; Research grant/Funding (self): Puma Biotechnology; Shareholder/Stockholder/Stock options: Gatekeeper; Licensing/Royalties, patent on EGFR mutations licensed to LabCorp: Dana-Farber Cancer Institute. All other authors have declared no conflicts of interest.
LBA62 - Efficacy and safety of patritumab deruxtecan (U3-1402), a novel HER3 directed antibody drug conjugate, in patients (pts) with EGFR-mutated (EGFRm) NSCLC
- Helena A. Yu (New York, United States of America)
Abstract
Background
There are few treatment options for pts with advanced
Methods
The dose escalation part was presented previously. The dose expansion part enrolled pts with
Results
As of 30 April 2020, 57 pts from dose escalation and dose expansion were treated at the 5.6 mg/kg dose, and 56 pts were evaluable for response. Among 28 pts continuing treatment at data cutoff, 6 had only 1 tumor evaluation. Median prior anticancer regimens for metastatic disease was 4 (range, 1-9); 51 pts [90%] received prior platinum. Median number of prior EGFR TKIs was 2 (range, 1-4); 49 pts [86%] received prior osimertinib. 27 pts (47%) had history of central nervous system metastases. Median treatment duration was 3.5 mo (range, 1-14 mo); median follow up was 5.4 mo (range, 0.3-15 mo). The most common grade ≥3 treatment-emergent adverse events were platelet count decrease (25%) and neutrophil count decrease (16%). Efficacy for the 56 efficacy-evaluable pts is shown below; 3 additional pts had PR awaiting confirmation. HER3 was expressed in nearly all tumors. Efficacy was observed in pts with various mechanisms of EGFR TKI resistance, including
Conclusions
Patritumab deruxtecan at 5.6 mg/kg provides promising evidence of preliminary antitumor activity and safety in heavily pretreated pts with locally advanced or metastatic Activity according to BICR evaluation (Efficacy-Evaluable Population) a22/56 (39%) patients had best percentage decrease in sum of tumor diameters ≥30%. BOR, best overall response; CR, complete response; DCR, disease control rate; DoR, duration of response; NE, not evaluable; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Dose escalation + dose expansion cohorts Confirmed BOR, n/N (%) CR 1/56 (2) PR 13/56 (23) SD 25/56 (45) PD 9/56 (16) NE 8/56 (14) Confirmed ORR, n/N (%) 95% CI 14/56 (25) (14.4-38.4) DCR, n/N (%) 95% CI 39/56 (70) (55.9-81.2) DoR (95% CI) median (range), months 7 (3.0-7.0)
Clinical trial identification
NCT03260491.
Editorial acknowledgement
Jessica R. Augello, Ashfield Healthcare Communications.
Legal entity responsible for the study
Daiichi Sankyo.
Funding
Daiichi Sankyo.
Disclosure
H.A. Yu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Cullinan; Research grant/Funding (institution): Lilly. K. Gold: Advisory/Consultancy: Rakuten; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Pharmacyclics; Research grant/Funding (self): BerGenBio; Research grant/Funding (self): Daiichi-Sankyo. H. Hayashi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca K.K.; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer Ingelheim Japan Inc; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Co. Ltd.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharmaceutical Co. Ltd.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly Japan K.K.; Speaker Bureau/Expert testimony: Kyorin Pharmaceutical; Speaker Bureau/Expert testimony: MSD K.K.; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Pfizer Japan Inc.; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co. Ltd.; Advisory/Consultancy: Shanghai Haihe; Advisory/Consultancy: Biopharm. M. Johnson: Research grant/Funding (institution): BerGenBio, Research grant/Funding (institution): Lilly, Research grant/Funding (institution): EMD Serono, Research grant/Funding (institution): Janssen, Research grant/Funding (institution): Mirati Therapeutics, Research grant/Funding (institution): Genmab, Research grant/Funding (institution): Pfizer, Research grant/Funding (institution): AstraZeneca, Research grant/Funding (institution): Genentech / Roche, Research grant/Funding (institution): Stemcentrix, Research grant/Funding (institution): Novartis, Research grant/Funding (institution): Checkpoint Therapeutics, Research grant/Funding (institution): Array BioPharma, Research grant/Funding (institution): Regeneron, Research grant/Funding (institution): Apexigen, Research grant/Funding (institution): AbbVie, Research grant/Funding (institution): Tarveda, Research grant/Funding (institution): Adaptimmune, Research grant/Funding (institution): Syndax, Research grant/Funding (institution): Neovia, Research grant/Funding (institution): Boehringer Ingelheim, Research grant/Funding (institution): Sanofi, Research grant/Funding (institution): Hengrui Therapeutics Inc., Research grant/Funding (institution): Merck, Research grant/Funding (institution): Daiichi - Sankyo, Research grant/Funding (institution): Lycera, Research grant/Funding (institution): G1 Therapeutics, Research grant/Funding (institution): Dynavax, Research grant/Funding (institution): Loxo, Research grant/Funding (institution): Cytomx, Research grant/Funding (institution): BeiGene, Research grant/Funding (institution): Birdie, Research grant/Funding (institution): Corvus, Research grant/Funding (institution): Incyte, Research grant/Funding (institution): Genocea, Research grant/Funding (institution): Gritstone, Research grant/Funding (institution): Amgen, Research grant/Funding (institution): Bristol Myers Squibb, Research grant/Funding (institution): Kadmon, Research grant/Funding (institution): Clovis, Research grant/Funding (institution): Acerta, Research grant/Funding (institution): OncoMed, Research grant/Funding (institution): Guardant Health, Research grant/Funding (institution): Takeda, Research grant/Funding (institution): Shattuck Labs, Research grant/Funding (institution): GlaxoSmithKline; Consulting/Advisory Role (spouse): Contract Lobbyist for Astellas, Consulting/Advisory Role (spouse): Contract Lobbyist for Otsuka Pharmaceuticals; Consulting/ advisory Role (self) - all to institution: Genentech/Roche, Consulting/ advisory Role (self) - all to institution: Celgene, Consulting/ advisory Role (self) - all to institution: Boehringer Ingelheim, Consulting/ advisory Role (self) - all to institution: Sanofi,Consulting/ advisory Role (self) - all to institution: Mirati, Consulting/ advisory Role (self) - all to institution: Loxo, Consulting/ advisory Role (self) - all to institution: Calithera, Consulting/ advisory Role (self) - all to institution: AstraZeneca, Consulting/ advisory Role (self) - all to institution: Merck, Consulting/ advisory Role (self) - all to institution: Araxes Pharma, Consulting/ advisory Role (self) - all to institution: Mersana Therapeutics, Consulting/ advisory Role (self) - all to institution: BeiGene, Consulting/ advisory Role (self) - all to institution: Incyte, Consulting/ advisory Role (self) - all to institution: Pfizer, Consulting/ advisory Role (self) - all to institution: Guardant Health, Consulting/ advisory Role (self) - all to institution: Bristol Myers Squibb, Consulting/ advisory Role (self) - all to institution: Ribon Therapeutics; Travel/Accommodation/Expenses: AbbVie, Travel/Accommodation/Expenses: Astellas, Travel/Accommodation/Expenses: AstraZeneca, Travel/Accommodation/Expenses: Boehringer Ingelheim, Travel/Accommodation/Expenses: Clovis, Travel/Accommodation/Expenses: Daiichi Sankyo, Travel/Accommodation/Expenses: EMD Serono, Travel/Accommodation/Expenses: Bristol Myers Squibb, Travel/Accommodation/Expenses: Exelixis, Travel/Accommodation/Expenses: Genentech, Travel/Accommodation/Expenses: Incyte, Travel/Accommodation/Expenses: Merck, Travel/Accommodation/Expenses: Pfizer, Travel/Accommodation/Expenses: Sysmex Inostics, Travel/Accommodation/Expenses: Vapotherm. M. Koczywas: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Celgene. H. Murakami: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Chugai Pharma; Speaker Bureau/Expert testimony: Lilly Japan; Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: MSD. M. Nishio: Speaker Bureau/Expert testimony, Research grant/Funding (self): Chugai Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Taiho Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer-Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (self): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo Healthcare; Research grant/Funding (self): Merck Serono; Research grant/Funding (self): Astellas. C. Steuer: Honoraria (self): AbbVie; Honoraria (self): Bergen Bio; Honoraria (self): Eli Lilly; Honoraria (self): Armo. J. Yang: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Celgene; Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Yuhan; Advisory/Consultancy: Hansoh; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Takeda Oncology; Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Eli Lilly. S. Karam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. Z. Qi: Full/Part-time employment: Daiichi Sankyo. S. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. C. Yu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. P.A. Jänne: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Acea Biosciences; Advisory/Consultancy: Ignyta; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Loxo Oncology; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly Pharmaceuticals; Advisory/Consultancy: Araxes Pharmaceuticals; Advisory/Consultancy: SFJ Pharmaceuticals; Advisory/Consultancy: Voronoi; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Advisory/Consultancy: Biocartis; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (self): Takeda Oncology; Advisory/Consultancy: Mirati Therapeutics; Shareholder/Stockholder/Stock options: Gatekeeper Pharmaceuticals; Research grant/Funding (self): Astellas Pharmaceuticals; Research grant/Funding (self): Puma; Research grant/Funding (self): Revolution Medicines; Licensing/Royalties: LabCorp. All other authors have declared no conflicts of interest.