Background

Irinotecan liposome plus 5-FU/LV is one of the standard therapy for metastatic pancreatic cancer(mPC) with failed to gemcitabine-based therapy. HR070803 is a liposome formulation of irinotecan and this study aimed to investigate the efficacy and safety of HR070803 plus 5-FU/LV versus placebo plus 5-FU/LV as the second-line treatment in patients with locally advanced pancreatic cancer(LAPC) or mPC who failed to gemcitabine-based therapy.

Methods

Patients (pts) were randomly assigned (1:1) to receive HR070803 56.5 mg/m² (based on irinotecan free base) plus 5-FU/LV 2000/200mg/m² (arm A) or placebo plus 5-FU/LV 2000/200mg/m² (arm B). Randomization was stratified by serum albumin level, treatment history of fluorouracil, treatment history of gemcitabine. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival(PFS), objective response rate(ORR) and safety profile, etc. The analysis was based on 228 deaths, with a cutoff date of Nov 18, 2021.

Results

From January 2018 to May 2021, 298 pts were randomly assigned. At a median follow-up of 12.81 months, the primary endpoint with mOS of 7.39 months (95%CI: 6.05-8.41) and 4.99 months (95%CI: 4.27-6.01) in arm A and arm B has met (HR =0.63, 96.4% CI: 0.48-0.84; P=0.0019). Secondary endpoint mPFS was 4.21 months (95%CI: 2.92-5.59) vs. 1.48 months (95%CI: 1.41-1.58) (HR =0.36, 95% CI: 0.27-0.48; P<0.0001), and ORR was 12.75% (95%CI: 7.86-19.20) vs. 0.67% (95%CI: 0.02-3.68) (P<0.0001). In the safety population of 296 pts, the most common grade ≥3 AEs in arm A were γ-GGT elevations (19.05%) and neutropenia (12.93%). The incidence of all grade and grade≥3 diarrhea was 45.58% and 4.08%, neutropenia was 33.33% and 12.93%, cholinergic syndrome was 1.36% and 0% in arm A.

Conclusions

HR070803 plus 5-FU/LV demonstrated a highly statistically significant and clinically meaningful improvement in OS in treatment of locally advanced or metastatic PC with prior gemcitabine-based therapy. Along with a manageable safety profile, these data suggest HR070803 plus 5-FU/LV is a new treatment selection for the population.

Clinical trial identification

NCT05074589.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

Background

Pancreatic carcinoma (PC) is an aggressive malignancy and the 4th cause of all cancer deaths worldwide. More than 30% of patients with PC are unresectable because of the local extension with a median overall survival (OS) of less than one year. Folfirinox (FFX) is superior to gemcitabine in the treatment of metastatic PC, in terms of OS and progression-free survival (PFS) but standard of care remains gemcitabine (gem) for LAPC.

Methods

Pts with histologically proven LAPC not suitable for surgery, WHO PS ≤1, no cardiac ischemia were eligible. Randomization was stratified by center, tumour localization (pancreas head yes/no), WHO PS (0 vs 1) and age (≤60yr vs > 60yr). Pts received FFX (every 14 days for 12 cycles) or Gem 1000 mg/m² on days 1, 8, and 15 for six 28-day cycles excepted for cycle 1 with an infusion at D22. Primary endpoint was PFS. Secondary endpoints were OS, percentage of secondary curative-intent surgery, objective response rate, disease control rate, time to treatment failure, quality of life and safety. A total of 170 pts (142 events) were needed to detect an increase of 3 months (mo) in PFS with 80% power (log-rank test, 5% 2-sided α). HR and 95% CI will be estimated by a stratified Cox proportional hazard model. PFS and OS outcomes will be presented in the intent-to-treat population.

Results

A total of 171 patients aged 35-84 years (yr) were included and followed for a maximum of 5 yr. With a median follow-up of 43.7 mo, 146 PFS events were observed and the median PFS was 9.8 mo (95% CI: 7.2; 11.7) with FFX vs 7.5 mo% (95% CI: 6.0 ; 9.2) with Gem, stratified HR=0,57 (95% CI: 0.3 ; 1.08), p=.0468. The median OS was 15.1 mo (95% CI: 11.9 ; 20.3) in FFX arm vs 15.6 mo (95% CI:11.7 ; 18.6) in Gem arm, stratified HR=1.03 (95% CI: 0.53 ; 1.98), p=0.66. FFX treatment was well tolerated. AEs of grade ≥ 3 were reported in 32 patients (38%) in Arm Gem and 35 in arm FFX (41%).

Conclusions

PRODIGE 29/NEOPAN trial results shows that FFX yields significantly longer PFS compared to Gem and was well tolerated. No significant difference in OS was observed between both groups. Other secondary endpoints are currently explored, and will be presented during ESMO meeting.

Clinical trial identification

NCT02539537.

Legal entity responsible for the study

Unicancer.

Funding

Institut National du Cancer (INCA).

Disclosure

M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck Kga, Pfizer, Bayer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Basilea, Sotio, Pierre Fabre, Bohringer, Rafael, Servier, Zymeworks, Ipsen, Bayer, Glaxo Smith Kline, HalioDX, Lilly; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Invited Speaker: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. F. Di Fiore: Financial Interests, Personal, Invited Speaker, Honoraria/Travel/Accomodation/Expenses: Roche, Amgen, Merck, Sanofi, Ipsen, Servier, Pierre Fabre; Financial Interests, Personal, Invited Speaker, Honoraria: Bayer, Novartis, Jenssen, Mylan, MSD, bms. P. Follana: Financial Interests, Personal, Invited Speaker: GSK, Eisai, MSD; Financial Interests, Personal, Expert Testimony: Clovis, Novartis; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Other, Congress invitation: GILEAD. J. Bachet: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche; Financial Interests, Personal, Other, Honoraria: Sanofi, Servier; Financial Interests, Personal, Invited Speaker: Viatris; Non-Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Funding: AstraZeneca. T. Lecomte: Financial Interests, Personal, Other, Honoraria: Sanofi, Merck, Servier, Amgen, Ipsen, Pierre Fabre, AstraZeneca, Deciphera, Bayer. F. El Hajbi: Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Servier, Merck, AAA. V. Ly Lebrun: Financial Interests, Personal, Other, Honoraria: IPSSEN. O. Bouche: Financial Interests, Personal, Other, Honoraria: Amgen, Apmonia, Therapeutics, Bayer, Merck, Pierre Fabre, Roche, Sanofi, Servier. All other authors have declared no conflicts of interest.

Background

Topaz-1 was the first phase-III study demonstrating efficacy for the PD-L1 inhibitor durvalumab (D) in combination with gemcitabine (Gem) and cisplatin (Cis), and the combination has the potential to become a new first-line standard of care in biliary tract cancers (BTCs). The aim of this proof-of-concept study was to evaluate the efficacy of tremelimumab (two dosing regimens) in combination with CTx+D.

Methods

IMMUCHEC was a prospective, randomized, multi-center phase II study. Adult patients with ECOG 0-1 and histologically confirmed metastatic BTC/gallbladder cancer were eligible. The primary endpoint was objective response rate (ORR) according to RECIST1.1 criteria in patients without prior systemic palliative CTx. Secondary endpoints were overall survival (OS) progression-free survival (PFS), and safety. Exploratory analysis included pooled efficacy and safety analysis of experimental treatment arms. The trial interventions: Arm A – D 1.5g Q3W + 4x T 75 mg Q3W + gem 1000mg/m²; Arm B - D 1.5g Q3W + 4x T 75 mg Q3W + Gem 1000mg/m² + Cis 25mg/m²; Arm C – control treatment Gem + Cis; Arm D − D 1.5g, Q3W + 1x bolus T 300 mg+ Gem + Cis; Arm E − D 1.5g Q3W + Gem + Cis.

Results

In total, 138 patients were randomized in 16 German centers. The relative distribution of anatomic subgroups (extrahepatic/intrahepatic/gallbladder) between arms: A – 21.7%/47.8%/30.4%; B – 25.0%/70.0%/5.0%; C – 26.7%/73.3%/0%; D – 13.8%/69.0%/17.2%; E – 11.1%/88.9%/0%, respectively, see the table. Correlative analysis of efficacy with genetic alterations, gene expression signatures and changes of immune cell populations will be reported. Table: 52MO

IMMUCHEC trial results

Conclusions

There was not definitive evidence of T adding substantial improvement over D alone in combination with CTx in 1^st line BTC. The omission of Cis was associated with an inferior outcome. There were no new safety signals.

Clinical trial identification

NCT03473574.

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

Funded by AIO-Studien-gGmbH supported by AstraZeneca.

Disclosure

A. Vogel: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Eisai, Ipsen, Incyte, PierreFabre, Lilly, Imaging Equipment Ltd (AAA), Roche, MSD, Beigene, Jiangsu Hengrui Medicines.; Financial Interests, Personal, Advisory Board: Roche, Bayer, BMS, MSD, Eisai, Ipsen, Incyte, PierreFabre, Lilly, AstraZeneca, Boston Scientific, Sirtex, Daiichi-Sankyo. S. Boeck: Financial Interests, Personal, Advisory Role: Fresenius, AstraZeneca, Servier, Incyte, Janssen-Cilag, MSD, BMS; Financial Interests, Personal, Invited Speaker: Servier, MSD. O. Waidmann: Financial Interests, Institutional, Research Grant: Merck, Else-Kröner-Fresenius-Stiftung; Financial Interests, Personal, Advisory Role: Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck, Serono, MSD, Novartis, Roche, Servier; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Ipsen, EISAI, BMS, MSD, Novartis, Roche; Financial Interests, Personal, Other, travel expenses: AbbVie, Bayer, BMS, Gilead, Ipsen, Medac, Merck. C. Springfeld: Financial Interests, Personal, Invited Speaker: Roche, Servier; Financial Interests, Personal, Advisory Board: MSD, Bayer, AstraZeneca, Eisai. R. Plentz: Financial Interests, Personal, Advisory Board: Servier, AstraZeneca, BMS, MSD, Ipsen, Roche, Bayer. C. Koehne: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Amgen, BMS, AstraZeneca; Financial Interests, Personal, Other, travel expenses: Merck; Financial Interests, Personal, Advisory Board: BMS, Merck, Amgen. All other authors have declared no conflicts of interest.

Background

Therapeutic options in pre-treated advanced biliary tract cancer (BTC) are limited. Although the ABC-06 trial demonstrated clinical benefit for mFOLFOX, there is an unmet need for more effective 2^nd line therapies. The aim of this study was to evaluate the efficacy of pegylated liposomal irinotecan formulation (nal-IRI)/5-FU/leucovorin (LV) compared to 5-FU/LV in 2^nd line BTC.

Methods

NALIRICC is a prospective, randomized, two-sided, phase II study. Pts > 18 years, with ECOG PS 0/1, histologically confirmed metastatic BTC and progression on 1^st line Gemcitabine-based therapy were eligible. Trial interventions were Arm A nal-IRI (80 mg/m²) plus 5-FU (2400 mg/m²)/LV (400 mg/m²), q2w or Arm B 5-FU/LV, q2w. Pts were stratified according to primary tumor site, and response was evaluated per RECIST v1.1, every 6 weeks. Primary endpoint (EP) was progression-free survival (PFS). Secondary EPs were overall survival (OS), overall response rates (ORR), safety and QoL (EORTC QLQ C30). This study was designed to improve median PFS from 1.5 months (P0) to 3 months (P1; HR 0.5) with 2-sided α of 0.05, power of 90.3%; 99 pts required in total.

Results

In total 100 pts were randomized in 17 German centers (49 pts: nal-IRI/5-FU/LV arm/ 51 pts: 5-FU/LV arm). 64/19/17 pts had intra-/extrahepatic/gallbladder cancers. Pt characteristics were well balanced between the two arms. Trial results see the table. Most common grade ≥3 Adverse Events in nal-IRI/5-FU/LV group were decreased neutrophil counts (16.6%), diarrhea (14.6%), and nausea (8.3%). 27.5% of patients in the 5-FU/LV groups received irinotecan-based therapies post-progression. QoL was similar between both arms. Table: 53MO

NALIRICC-Trial results, median follow-up of 5,9 months

Conclusions

The NALIRICC-trial did not meet its primary EP. The addition of nal-IRI to 5-FU/LV did not improve PFS or OS compared to 5-FU/LV alone and was associated with higher toxicity. 5FU/LV may be considered as a reasonable alternative in 2^nd line advanced BTC.

Clinical trial identification

NCT03043547.

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

AIO-Studien-gGmbH supported by Servier.

Disclosure

A. Vogel: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Eisai, Ipsen, Incyte, PierreFabre, Lilly, Imaging Equipment Ltd (AAA), Roche, MSD, Beigene, Jiangsu Hengrui Medicines.; Financial Interests, Personal, Advisory Board: Roche, Bayer, BMS, MSD, Eisai, Ipsen, Incyte, PierreFabre, Lilly, AstraZeneca, Boston Scientific, Sirtex, Daiichi-Sankyo. G. Folprecht: Financial Interests, Personal, Invited Speaker: Roche / Genentech, Falk Foundation, Lilly; Financial Interests, Personal, Advisory Board: Sanofi-Aventis, Merck, BMS, MSD, Servier, Pierre Fabre, Roche / Genentech, Bayer, Exact Sciences. A. Kretzschmar: Financial Interests, Personal, Advisory Role: Servier, Roche, BMS, MSD, Merck, Sanofi. N. Ziegenhagen: Financial Interests, Institutional, Sponsor/Funding, Clinical Trial: Pfizer, Boehringer Ingelheim, MSD Sharp & Dohme GmbH, Astellas Pharma, Amgen; Non-Financial Interests, Institutional, Member, Membership: ESMO. S. Boeck: Financial Interests, Personal, Project Lead: Incyte; Financial Interests, Institutional, Sponsor/Funding, Clinical Trial: Servier. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar, BMS, EUSA-Pharma, PharmaMar, Lilly, Roche; Financial Interests, Institutional, Advisory Board: Roche, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Other, scientific lead of a trial with funding from Novartis: Novartis; Non-Financial Interests, Member: ASCO, Deutsche Krebsgesellschaft - German Cancer Society (DKG), Connective Tissue Oncology Society (CTOS), Deutsche Sarkomstiftung (DSS). T.O. Götze: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Foundation Medicine, Lilly, MCI, MSD Sharp Dohme, Novartis, Roche, Sanofi, Aventis, Servier; Financial Interests, Personal, Project Lead: Lilly, AstraZeneca, Incyte, DGF German Research Foundation, GBA Gemeinsamer Bundesausschuss, Deutsche Krebshilfe. E. Goekkurt: Financial Interests, Institutional, Advisory Board: BMS, Daiichi Sankyo, MSD; Financial Interests, Institutional, Principal Investigator, local PI: AstraZeneca, BMS, Daiichi Sankyo, MSD, Novartis. U. Graeven: Financial Interests, Personal, Stocks/Shares: Biontech; Financial Interests, Personal, Advisory Role, Honoraria: Boehringer Ingelheim, Amgen, AstraZeneca, BMS, MSD Oncology, Sanofi Aventis, Fujifilm, Novartis; Financial Interests, Personal, Other, Travelexpenses: Merck KGaA, Amgen, Boehringer Ingelheim, GSK. A. Saborowski: Financial Interests, Personal, Advisory Role: Roche, BMS, Falk Foundation, Servier. All other authors have declared no conflicts of interest.

Background

The ABC-06 clinical trial stablished ASC+mFOLFOX as the standard of care treatment after Cisplatin and Gemcitabine (CisGem) for ABC but its impact on QoL has not been reported.

Methods

Within the ABC-06 study, patients (pts) diagnosed with ABC with progression after CisGem were randomised (1:1) to ASC+mFOLFOX or ASC. QoL (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-30, QLQ-BIL21) and V-He (Euroqol EQ5D) questionnaires were completed at baseline and 12-weekly thereafter. Pateints who completed all or part of the EORTC or EQ-5D measure at baseline (BSL) were elegible. Follow-up data is reported for month 4 (M4) (follow-up visit that occurred up to 120 days post screening). Descriptive analyses,of the QoL measures by study arm are reported here; T-test was used for comparison between time-points (two-tailed p-value <0.05 was considered statistically significant).

Results

Out of 162 pts randomised, 138 were eligible for this available case analysis (65 ASC arm, 73 ASC+FOLFOX arm). Baseline characteristics and time from BSL to M4 visit were well balanced between both study arms. Addition of FOLFOX to ASC did not appear to induce worsening of the QOL parameters assessed (Table). In contrast, pts in the ASC-alone arm appeared to experience worsening of the EQ-5D utility values, and most of the QLQ-30 scales (including global, physical, social and role scales). There also appeared to be worsening of nausea and pain which remained stable in the ASC+FOLFOX arm. Table: 54MO

Conclusions

For ABC patients, treatment with second-line ASC+mFOLFOX may allow stabilisation of QoL scales and avoid worsening of nausea and pain at 4 months after baseline assessment. Full analyses of QoL to explore this potentially positive impact of FOLFOX is ongoing, along with an assessment of whether FOLFOX may be cost-effective.

Clinical trial identification

NCT01926236.

Legal entity responsible for the study

The Christie NHS Foundation Trust.

Funding

Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research.

Disclosure

A. Lamarca: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Ipsen, Incyte, AAA, QED, QED, AstraZeneca, EISAI, Servier, Incyte; Financial Interests, Personal, Advisory Board: EISAI, Nutricia, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca; Financial Interests, Institutional, Other, Access to FM molecular profiling: Roche; Non-Financial Interests, Principal Investigator, PI of trial: QED, Merck; Other, Other, Travel and educational support: Ipsen, Pfizer, Bayer, AAA, SIrTex, Novartis, Mylan, Delcath. All other authors have declared no conflicts of interest.

Background

No study up until now has evaluated the efficacy of immune checkpoint inhibitors combined with chemotherapy as 2^nd line treatment of advanced gastric/gastro-oesphageal junction (GEJ) adenocarcinoma.

Methods

DURIGAST PRODIGE 59 is a randomized, multicenter, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI plus durvalumab (anti-PD-L1) (FD) versus FOLFIRI plus durvalumab and tremelimumab (anti-CTLA-4) (FDT). Key eligibility criteria included advanced gastric/GEJ adenocarcinoma, platinum-based first-line chemotherapy and ECOG performance status 0 or 1. The primary endpoint is progression-free survival (PFS) at 4 months, which was expected to be 70%. Secondary endpoints included safety, overall survival (OS) and quality of life.

Results

Between August 2020 and June 2021, 96 patients were randomized, 48 in each arm. The median age was 59.7 years, 30.4% were women and 66.3% were ECOG PS 1. Half of patients had gastric tumors (50.0%), mostly with synchronous metastases (65.2%) and doublet first-line chemotherapy (63.0%). Only 4.3% were dMMR/MSI. The 4-month PFS were 44.7% [90%CI: 32.3–57.7] and 55.6% [90%CI: 42.3–68.3] in the FD and FDT arms, respectively. Median PFS were 3.8 and 5.4 months, objective response rates were 32.6% and 37.7% and median OS was 13.3 and 9.5 months in FD and FDT arms, respectively. However, a remarkable disease control over 1 year was observed in FDT arm (n=7, 15.2%) as compared FD arm (n=2, 4.3%). Grade 3-4 adverse events related to the treatment were 47.8% in each arm (asthenia: 17.4% vs 23.9%, neutropenia: 15.2% vs 23.9%, anemia: 10.9% vs 6.5%, diarrhea: 2.2% vs 10.9% and vomiting: 6.5% vs 2.2% in FD and FDT arms, respectively).

Conclusions

Combination of immune checkpoint inhibitors plus FOLFIRI in 2^nd line treatment for advanced gastric/GEJ adenocarcinoma demonstrates an acceptable safety profile. Despite a negative result for the entire population, this combination seems to be very active in a sub-group of patients. Predictive factors of efficacy are currently explored, and will be presented during ESMO meeting.

Clinical trial identification

NCT03959293.

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

This research was funded by Fédération Francophone de Cancérologie Digestive (FFCD). DURIGAST PRODIGE 59 was funded in part by AstraZeneca and FFCD is funding the biobank and molecular analysis.

Disclosure

D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Pierre Fabre, BMS, Servier; Financial Interests, Personal, Invited Speaker: MSD, Sanofi, AMGEN. O. Bouche: Financial Interests, Personal, Advisory Board: amgen, apmonioa therapeutics, bayer, merck serono, pierre fabre, roche, sanofi, servier. P. Artru: Financial Interests, Personal, Advisory Board: Servier, Pierre Fabre, Bayer, MSD, Amgen, Roche. C. Louvet: Financial Interests, Personal, Advisory Board: MSD, Roche, Servier, Amgen. All other authors have declared no conflicts of interest.

Background

Primary results of DESTINY-Gastric02 (NCT04014075; data cutoff [DCO] April 9, 2021), a single-arm, phase II trial of T-DXd in Western pts with HER2+ gastric/GEJ cancer, demonstrated a confirmed objective response rate (cORR) of 38.0% (95% CI, 27.3-49.6), and safety consistent with the established T-DXd safety profile. We report OS and updated efficacy and safety.

Methods

Pts with centrally confirmed HER2+ (IHC3+ or IHC2+/ISH+ biopsy after progression on trastuzumab-based therapy) unresectable/metastatic gastric/GEJ cancer who progressed on or after 1L therapy received T-DXd 6.4 mg/kg Q3W. The primary endpoint was cORR per RECIST v1.1 by independent central review (ICR). Progression-free survival (PFS) by ICR, duration of response (DOR) by ICR, OS, and patient-reported outcomes based on the European Organization for Research and Treatment of Cancer 5-dimension 5-levels (EQ-5D-5L) quality-of-life (QoL) and Functional Assessment of Cancer Therapy-Gastric (FACT-GA) questionnaires were secondary endpoints.

Results

At DCO (November 8, 2021), 79 pts from the US/EU had received T-DXd. 76 pts (96.2%) had received 1 prior line of therapy and 3 (3.8%) had received 2 lines. With a median duration of follow up of 10.2 mo, 10 pts (12.7%) remained on treatment. Median OS was 12.1 mo (95% CI, 9.4-15.4); landmark 12-mo OS rate was 50.6%. cORR was 41.8% (33/79; 4 complete and 29 partial responses). Median DOR was 8.1 mo (95% CI, 5.9-NE). Median PFS was 5.6 mo (95% CI, 4.2-8.3). All pts experienced ≥1 treatment-emergent adverse event (TEAE); 55.7% experienced grade ≥3 TEAEs. The most common TEAEs were nausea (67.1%), vomiting (44.3%) and fatigue (57.0%). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 pts (10.1%); 6 (7.6%) had grade 1-2 and 2 (2.5%) had grade 5. At DCO (April 9, 2021), QoL assessed by EQ-5D-5L and FACT-GA had been maintained over the treatment course.

Conclusions

T-DXd continues to demonstrate substantial clinical benefit and a tolerable safety profile in 2L+ Western pts with HER2+ unresectable/metastatic gastric/GEJ cancer.

Clinical trial identification

NCT04014075.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Marianna Johnson, PhD, Rachel Hood, PhD, and Laura Halvorson, PhD of ApotheCom and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

G.Y. Ku: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, IMAB, Merck, Pieris, Zymeworks; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, CARSgen, IMAB, Merck, Pieris, Zymeworks. M. Di Bartolomeo: Financial Interests, Personal, Advisory Board, Consultant: Lilly; Financial Interests, Personal, Advisory Board, consultant: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Institutional, Other, Research founding: Lilly spa; Financial Interests, Institutional, Invited Speaker: MSD, BMS, AstraZeneca, Daiichi, Incyte. E. Smyth: Financial Interests, Personal, Invited Speaker: Amgen, Bristol-Myers Squibb, Imedex, Merck, Novartis, Prova Education, Servier, TouchIME; Financial Interests, Personal, Other, TSC: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol-Myers Squibb, My Personal Therapeutics, Novartis, Roche, Servier, Zymeworks; Financial Interests, Personal, Other, IDMC: Beigene, Zymeworks; Financial Interests, Personal, Expert Testimony: Bristol-Myers Squibb; Financial Interests, Personal, Other, IDMC chair: Everest Clinical Research; Financial Interests, Personal, Officer: EORTC GI Clinical Trials Group; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Roche, AstraZeneca, Merus, Basilea, MSD; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb. I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli-Lilly, MSD, Roche, Merck Serono, AstraZeneca, OncXerna, Pierre Fabre, Boehinger Ingelheim, Astella, Incyte, GSK, Sotio, Daiichi-Sankyo, Eisai; Financial Interests, Personal, Other, DMC chairman: Five Prime Therapeutics; Financial Interests, Personal, Invited Speaker: Eisai, Eli-Lilly, Servier; Financial Interests, Institutional, Invited Speaker: Cilag-Janssen, Eli Lilly. H. Park: Financial Interests, Institutional, Research Grant: Adlai Nortye USA, Alpine Immune Sciences, Ambryx, Amgen, Aprea Therapeutics AB, Array BioPharma, Bayer, BeiGene, BJ Bioscience, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Elicio Therapeutics, EMD Serono, Exelixis, Genentech, Gilead Sciences, GlaxoSmithKline, Grossamer Bio, Hoffman-LaRoche, Hutchison, MediPharma, ImmuneOncia Therapeutics, Incyte, Jounce Therapeutics, Mabspace Biosciences, MacroGenics, Medimmune, Medivation, MERCK, Milennium, Mirati Therapeutics, Novartis, Oncologie, Pfizer, PsiOxus Therapeutics, Puma Biotechnology, Regeneron, RePare Therapeutics, Seattle Genetics, Synermore Biologics, Taiho Pharmaceutical, TopAlliance Biosciences, Turning Point Therapeutics, Vedanta Biosciences, Xencore Inc. S. Siena: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bayer, BMS, CheckmAb, Daiichi-Sankyo, Guardant Health, Menarini, Merck, Novartis, Roche-Genentech, Seagen. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol -Myers Squibb. Z.A. Wainberg: Financial Interests, Personal, Other, Honoraria: Amgen, Astra Zenica, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Array; Financial Interests, Personal, Advisory Board: Amgen, Astrazenica, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Array; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Daiichi Sanyko, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Roche/Genentech, Array/Pfizer. J.A. Ajani: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, AstraZenica; Financial Interests, Institutional, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. J. Chao: Financial Interests, Personal, Advisory Board: Merck, Amgen, Daiichi Sankyo, Macrogenics, Bristol Myers Squibb, Astellas, Turning Point Therapeutics; Financial Interests, Personal, Invited Speaker: Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting: Lilly, AstraZeneca, Ono Pharmaceuticals, Roche; Financial Interests, Institutional, Funding: Merck, Brooklyn Immunotherapeutics. F. Barlaskar: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Kawaguchi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. A. Qin: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Singh: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. G. Meinhardt: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Bayer Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. E. Van Cutsem: Financial Interests, Personal, Advisory Board, Advisory board and/or Speaking: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabr; Financial Interests, Institutional, Funding, research grant paid to institution: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier.