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Displaying One Session

Channel 3 Proffered Paper session
Date
20.09.2020
Time
16:20 - 18:00
Room
Channel 3
Chairs
  • Christophe Massard (Villejuif, CEDEX, France)
  • Giulio Draetta (Houston, United States of America)
Proffered Paper - Developmental therapeutics Proffered Paper session

524O - Initial results of a phase I study of MK-4830, a first-in-class anti–immunoglobulin-like transcript 4 (ILT4) myeloid-specific antibody in patients (pts) with advanced solid tumours

Presentation Number
524O
Lecture Time
16:20 - 16:32
Speakers
  • Lillian L. Siu (Toronto, Ontario, Canada)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00

Abstract

Background

MK-4830 is a novel, first-in-class human IgG4 monoclonal antibody targeting the myeloid-specific ILT4 receptor. MK-4830 catalyzes reprogramming of tumour-associated macrophages, relieving myelosuppression and enhancing T cell function. We present data from the first-in-human phase I dose escalation study (NCT03564691) of MK-4830 and MK-4830 + pembrolizumab (pembro).

Methods

Pts with advanced solid tumours received MK-4830 IV Q3W at escalating doses alone and with pembro. Primary end points were safety and tolerability. PK was a secondary end point; exploratory objectives included ORR per RECIST v1.1, evaluation of receptor occupancy (RO), and immune correlates of response in blood and tumour.

Results

Among 84 pts, 50 received MK-4830 monotherapy; 34 received MK-4830 + pembro. Median age was 62 years; 50% previously received ≥3 lines of therapy. No dose-limiting toxicities were observed; maximum-tolerated dose was not reached. Any-grade AEs were consistent with those common to pembro. Treatment-related AEs were reported in 52% of pts; most were grade 1/2. MK-4830 steady-state serum PK at Ctrough was achieved at the highest dose levels, at which almost all pts had ≥95% blood RO. Preliminary efficacy data show 11 objective responses, with 2 complete responses and 9 partial responses; 1 response was observed in a patient receiving MK-4830 monotherapy. All responses occurred in heavily pretreated pts, 5 of whom had not had a response to prior anti–PD-1 therapy. Responses were durable; some pts received >1 year of treatment. Pre- and on-treatment (n=15) biopsies enabled a preliminary assessment of correlation between RO and immune cell subsets before and during treatment.

Conclusions

This first-in-class MK-4830 antibody targeting ILT4 given as monotherapy and in combination with pembro was well tolerated and showed dose-related evidence of target engagement. Durable responses were observed with both MK-4830 alone and with MK-4830 + pembro in heavily pretreated pts, 5 of whom progressed on prior anti–PD-1 therapies. These initial data support the further development of MK-4830 + pembro for pts with advanced solid tumors.

Clinical trial identification

NCT03564691.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Holly C. Cappelli and Dana Francis of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

L.L. Siu: Honoraria (institution): Arvinas; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Officer/Board of Directors: AACR; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/Medimmune; Advisory/Consultancy: MorphoSys; Advisory/Consultancy: Roche; Research grant/Funding (institution): Roche/Genetech; Advisory/Consultancy: Loxo; Advisory/Consultancy: Oncorus; Advisory/Consultancy, Research grant/Funding (institution): Symphogen; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Voronoi; Advisory/Consultancy: Treadwell Therapeutics; Advisory/Consultancy: Tessa; Advisory/Consultancy: Navire; Advisory/Consultancy: Relay Therapeutics; Advisory/Consultancy: Rubius Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Intensity Therapeutics; Research grant/Funding (institution): Mirati, Shattucks, and Avid. R. Geva: Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses: Medison; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Janssen; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: BOL Pharma; Travel/Accommodation/Expenses: Merck. D. Rasco: Research grant/Funding (institution): Merck. A.K. Abraham: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. J.F. Markensohn: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. L. Suttner: Full/Part-time employment: Merck; Research grant/Funding (self): GlaxoSmithKline. S. Siddiqi: Full/Part-time employment: Merck. R.A. Altura: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. C. Maurice-Dror: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Medison; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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Proffered Paper - Developmental therapeutics Proffered Paper session

525O - A phase I dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies

Presentation Number
525O
Lecture Time
16:32 - 16:44
Speakers
  • Geoffrey Ku (New York, NY, United States of America)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00

Abstract

Background

Anticalin® proteins are recombinant human proteins based on lipocalins. PRS-343, a first-in-class bispecific antibody-Anticalin fusion protein, targets HER2 and costimulatory immune receptor 4-1BB on T cells. Here, we report the results of a phase I trial in patients with HER2+ solid tumors.

Methods

PRS-343 was evaluated in sequential dose cohorts from 0.0005 to 18 mg/kg i.v. Doses were administered Q3W up to 8mg/kg, while doses at 8mg/kg were also given Q2W and Q1W and doses beyond 8mg/kg were administered Q2W. Primary study objectives included safety, tolerability and RP2D. Secondary objectives included ORR and DCR, PD response and PK profile. PD response (CD8+ T cell IHC) was assessed in tumor biopsies pre-/post-treatment.

Results

70 patients enrolled (median age 61 years, 59% female, 83% Caucasian, median of four lines of prior therapy) with GC/GEJ (n=25); BC (n=16); gynecological cancer (n=6); CRC (n=10); BTC (n=5); UC (n=2); melanoma, pancreatic and salivary duct cancer (n=1 each) were treated with PRS-343. Based on PK analyses and kinetics of the CD8+ T cell expansion post-treatment, the minimal active dose was considered to be 2.5 mg/kg. 33 patients treated at active dose levels were evaluable for response with an ORR and DCR of 12% and 52% (3% CR, 9% PR, 40% SD), respectively. All objective responses were observed on the Q2W schedule, at/above doses of 8mg/kg; ORR was 40% and DCR was 70% (10% CR, 30% PR). At active doses, we observed pronounced post-treatment expansion of CD8+ T cells while there was no increase at doses below 2.5mg/kg. This effect was more pronounced in patients with a confirmed PR or prolonged SD. PRS-343 was well tolerated and the most frequent TRAEs were mild to moderate infusion related reaction (25%), nausea (7%), arthralgia (5%), vomiting (4%), chills (4%), and fatigue (4%). No DLT was noted. We will also present results of a PRS-343/atezolizumab combination trial in HER2+ solid tumors.

Conclusions

PRS-343 is the first 4-1BB bispecific to demonstrate encouraging evidence of safety and clinical benefit with a correlative PD effect. Based on these data, a phase II trial in gastric/GEJ cancer has been planned in combination with ramucirumab and paclitaxel.

Clinical trial identification

NCT03330561.

Legal entity responsible for the study

Pieris Pharmaceuticals.

Funding

Pieris Pharmaceuticals.

Disclosure

M. Zettl: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. K. Aviano: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. L. Mar: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. P. Jolicoeur: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. S. Olwill: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Pieris Pharmaceuticals. I. Bruns: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Pieris Pharmaceuticals. All other authors have declared no conflicts of interest.

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Proffered Paper - Developmental therapeutics Proffered Paper session

526O - High activity of nivolumab in patients with pathogenic exonucleasic domain POLE (edPOLE) mutated Mismatch Repair proficient (MMRp) advanced tumours

Presentation Number
526O
Lecture Time
16:44 - 16:56
Speakers
  • Benoit J. Rousseau (Créteil, CEDEX, France)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00

Abstract

Background

Hotspot edPOLE mutations (mut) generate proofreading defects and hypermutated genomic profiles. While rare in the advanced setting, most edPOLE mut pathogenicity and derived sensitivity to anti-PD-1 (aPD1) agents remains unclear. We aimed to investigate the efficacy of nivolumab in MMRp tumours with edPOLE mut.

Methods

ACSé immunotherapy is a nationwide program launched by the French National Cancer Institute (INCa) and sponsored by the French network of comprehensive cancer centres (Unicancer) investigating the efficacy and tolerance of aPD1 in multiple phase II single arm cohorts in rare tumours. We report here the initial results of the edPOLE cohort, which is the first trial selecting patients on a prospective assessment of missense POLE mut pathogenicity by an ad hoc molecular tumour board. nivolumab (240 mg IV q2w) was administered until disease progression (PD), toxicity or for up to 2 years. The primary endpoint was the objective response rate (ORR) assessed by RECIST v1.1 at 12 weeks.

Results

From Apr 2018 to Jan 2020, 15 pts (mean age, 59 years) were included with colorectal (6), endometrial (4), gastric (2), pancreas (1), biliary (1) and glial (1) tumours. Mean number of previous lines of treatment was 2.7. Median follow up was 74 days (Q1-Q3= 40.5-188.5). At the date of submission, nivolumab safety was in accordance with data reported in other tumour types. ORR at 12 weeks in 10 evaluable patients was 30% (PR: n=3; SD: n=4; PD: n=3). Pathogenicity of edPOLE mut was confirmed by the ad hoc committee in 7 cases (47%): 2 P286R, 2 N363K, 2 V411L, 1 A463V. In the pathogenic mut group, ORR was 50% (3/6), disease control rate was 83% (5/6) and median progression-free survival (mPFS) was 161 days. Responses were observed in MMRp colorectal and endometrial cancers with P286R and V411L mutations. Conversely, in the non-pathogenic group (n=4), only 2 SD were observed as best response and 2 pts died before first evaluation. mPFS in this group was 47 days.

Conclusions

We report the first clinical trial assessing aPD1 in POLE mutated MMRp tumours. Nivolumab activity appears promising in edPOLE mutated MMRp advanced cancer pts but activity is limited to pathogenic mutations, underlining the need for individual mutational functional assessment by a molecular tumour board. We will include the tumour evaluation of the last 5 additional patients at the ESMO 2020 Virtual Congress.

Clinical trial identification

NCT03012581.

Legal entity responsible for the study

UNICANCER.

Funding

BMS.

Disclosure

B.J-C. Rousseau: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: Servier; Travel/Accommodation/Expenses: Astellas; Speaker Bureau/Expert testimony: Gilead. V. Simmet: Honoraria (self): Lilly; Honoraria (self): Servier; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Novartis. D. Pouessel: Honoraria (self): Ipsen; Honoraria (self), Honoraria (institution): BMS; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: AstraZenca; Honoraria (self): Sanofi; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Merck; Honoraria (self): Astellas; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (institution): MSD; Honoraria (institution): Incyte. A. Bruyas: Speaker Bureau/Expert testimony: BMS. F. Rolland: Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS. E. Saada-Bouzid: Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS. R. Cohen: Honoraria (self): Servier; Honoraria (self): Amgen; Honoraria (self): Sanofi. O. Bouche: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Merck; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Servier; Travel/Accommodation/Expenses: Lilly. A. Marabelle: Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Lytix pharma; Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca/Medimmune; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Chugai; Advisory/Consultancy: GSK; Advisory/Consultancy: Innate pharma; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bayer. All other authors have declared no conflicts of interest.

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Proffered Paper - Developmental therapeutics Proffered Paper session

Invited Discussant 524O, 525O and 526O

Lecture Time
16:56 - 17:06
Speakers
  • Antoine Italiano (Bordeaux, CEDEX, France)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00
Proffered Paper - Developmental therapeutics Proffered Paper session

Q&A and live discussion

Lecture Time
17:06 - 17:16
Speakers
  • Christophe Massard (Villejuif, CEDEX, France)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00
Proffered Paper - Developmental therapeutics Proffered Paper session

527O - CC-90010, a reversible, oral bromodomain and extra-terminal (BET) inhibitor in patients (Pts) with advanced solid tumours (STs) and relapsed/refractory (R/R) non-Hodgkin lymphoma: Updated results of a phase I study

Presentation Number
527O
Lecture Time
17:16 - 17:28
Speakers
  • Victor Moreno Garcia (Madrid, Spain)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00

Abstract

Background

BET proteins are epigenetic readers implicated in cancer pathogenesis. CC-90010 is a potent BET inhibitor that showed promising clinical activity in pts with advanced malignancies.

Methods

CC-90010-ST-001 is a phase I dose-escalation (part A) and -expansion (part B) study of CC-90010 in pts with advanced STs and R/R diffuse large B-cell lymphoma (DLBCL). Eleven dose levels (DLs) and 4 dosing schedules (2 weekly [2 d on/5 d off; 3 d on/4 d off], 1 biweekly [3 d on/11 d off], and 1 monthly [4 d on/24 d off]) were evaluated. Primary objectives were to determine safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory objectives were to assess antitumor activity, pharmacokinetics, and pharmacodynamics (PD).

Results

As of 7 Feb 2020, 84 pts were enrolled. In part A, 67 pts had advanced STs and 2 had R/R DLBCL. In part B, 13 pts had R/R DLBCL (1 pt was not treated until after the data cutoff), and 2 had advanced STs. MTDs were identified for 3 of the 4 dosing schedules. The RP2Ds were 30 mg 3 d on/11 d off and 45 mg 4 d on/24 d off. Six pts from part A had dose-limiting toxicities, in all dosing schedules. The most common grade 3/4 treatment-related adverse event (TRAE) was thrombocytopenia (part A=16%, part B=64%). Eight pts (12%) in part A and 4 pts (29%) in part B had serious TRAEs. In part A, 1 pt with progressive grade 2 astrocytoma had a complete response (CR; ongoing in cycle 19), and 1 pt with advanced endometrial carcinoma had a partial response (PR); 10 pts had stable disease (SD) ≥4 cycles, 3 had prolonged SD (19, 20, and 24 mo). In part B, 2 pts with R/R DLBCL had responses (CR and PR). Plasma exposures increased in an ∼ dose-proportional manner across DLs. The terminal half-life (t1/2) of CC-90010 was ∼60 h. CC-90010 induced ≥50% decrease of the PD biomarker CCR1 at doses ≥25 mg 4 h post last dose.

Conclusions

CC-90010 was well tolerated and showed antitumor activity in heavily pretreated pts with advanced malignancies. The long t1/2 and favorable PD profile improved tolerability and enabled less frequent dosing. These results support further evaluation of CC-90010 in STs and R/R DLBCL.

Clinical trial identification

Study ID: CC-90010-ST-001 NCT03220347; 2015-004371-79 (EudraCT Number).

Editorial acknowledgement

Tisheeka Graham-Steed, PhD BioConnections, LLC.

Legal entity responsible for the study

Celgene Corporation.

Funding

Celgene Corporation.

Disclosure

V. Moreno: Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pieris; Advisory/Consultancy: Janssen. I. Braña: Research grant/Funding (self): Celgene, A Bristol-Myers Squibb Company. J.M. Sepulveda Sanchez: Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy: Celgene, A Bristol-Myers Squibb Company; Advisory/Consultancy: GW Pharma; Speaker Bureau/Expert testimony: Astellas; Travel/Accommodation/Expenses: Ipsen. M. Vieito: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Debio; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck-Serono. O. Saavedra: Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Kyowakirin. C. Carlo-Stella: Honoraria (self): Bristol Myers Squibb; Honoraria (self), Speaker Bureau/Expert testimony: MSD; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): ADCT; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Sanofi; Research grant/Funding (self): Novartis; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Takeda. J-M. Michot: Honoraria (self): Celgene, A Bristol-Myers Squibb Company; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Janssen. A. Italiano: Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Springworks; Advisory/Consultancy: Epizyme; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Merck; Research grant/Funding (self): MSD; Research grant/Funding (self): Pharmamar. G. Musuraca: Advisory/Consultancy: Servier. R. Sarmiento: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. B. Amoroso: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company; Advisory/Consultancy: NordicNanovector; Advisory/Consultancy: ArgenX. T. Sánchez-Pérez: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Genentech/Roche. B. Hanna: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. A. Pinto: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Celgene, A Bristol Myers Squibb Company; Honoraria (self): Servier; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Takeda. All other authors have declared no conflicts of interest.

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Proffered Paper - Developmental therapeutics Proffered Paper session

528O - CC-90011 in patients (Pts) with advanced solid tumours (STs) and relapsed/refractory non-Hodgkin lymphoma (R/R NHL): Updated results of a phase I study

Presentation Number
528O
Lecture Time
17:28 - 17:40
Speakers
  • Antoine Hollebecque (Villejuif, France)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00

Abstract

Background

CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1A. CC-90011 was well tolerated and had promising antitumor activity in pts with advanced unresectable STs and R/R NHL in the dose-escalation part of the CC-90011-ST-001 study. Here we present updated results from the cohort expansion part of the study.

Methods

Pts in this phase I, dose-escalation (part A) and -expansion (part B), first-in-human study received CC-90011 once/wk (QW) in 28-d cycles. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy.

Results

Sixty-six pts enrolled, 50 in part A (27 with neuroendocrine neoplasms [NENs] and 1 with R/R NHL) and 16 in part B (all with NENs). The RP2D was 60 mg QW. As of 17 Jan 2020, 4 pts (3 with NENs, 1 with R/R NHL) in part A and 2 pts in part B remained on treatment (tx). The primary reason for tx discontinuation was progressive disease (part A, n=38 [76%]; part B, n=12 [75%]). Thrombocytopenia was the most common tx-related adverse event (AE; 47%), and the only serious AE reported in >1 pt in either part of the study; this on-target toxicity was reversible and manageable. AEs led to discontinuation in 3 pts (6%), all in part A. Two pts in part A and 1 in part B died due to underlying disease; there were no deaths due to tx-related AEs. Clinical benefit rate (partial or complete response [CR] or stable disease [SD] ≥4 mo) was 20% (95% CI, 10.0-33.7) in part A and 44% (95% CI, 19.8-70.1) in part B. In part A, the R/R NHL pt achieved a CR (ongoing in cycle 32) and 5 pts with NENs had SD ≥9 cycles, including 2 with SD ≥21 cycles. In part B, 3 pts with NENs had SD ≥9 cycles. Exposure increased proportional to dose. Negligible accumulation of exposure occurred with repeat dosing and systemic exposures at the same dose were similar in parts A and B. Decreased levels of chromogranin A and peripheral blood PD biomarker, MMD, indicated CC-90011 target engagement.

Conclusions

CC-90011 was well tolerated with favorable PK/PD profiles. Promising antitumor activity was observed in pts with NENs and R/R NHL.

Clinical trial identification

Study ID: CC-90011-ST-001 NCT02875223.

Editorial acknowledgement

Tisheeka Graham-Steed, PhD BioConnections, LLC.

Legal entity responsible for the study

Celgene Corporation.

Funding

Celgene Corporation.

Disclosure

A. Hollebecque: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Honoraria (institution): Eisai; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Debiopharm; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Medimmune. J.S. de Bono: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sierra Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genmab; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Menarini Silicon Biosystems; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Orion; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho; Research grant/Funding (institution): Cellcentric; Research grant/Funding (institution): Celgene, a Bristol-Myers Squibb Company. R. Plummer: Advisory/Consultancy: Pierre Faber; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Octimet; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Karus Therapeutics; Advisory/Consultancy: Biosceptre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Ellipses; Advisory/Consultancy: CV6 Therapeutics; Advisory/Consultancy: Astex Therapeutics; Advisory/Consultancy: Sanofi Aventis; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Speaker Bureau/Expert testimony: Tesaro; Travel/Accommodation/Expenses: MSD. G. Curigliano: Honoraria (self): Ellipsis; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Samsung; Speaker Bureau/Expert testimony: PRIME ; Speaker Bureau/Expert testimony: Accademia Nazionale di Medicina; Speaker Bureau/Expert testimony: MedScape. V. Moreno: Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pieris; Advisory/Consultancy: Janssen. F. de Braud: Advisory/Consultancy: TizianaLife Sciences; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene, A Bristol-Myers Squibb Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Servier; Advisory/Consultancy: Pharm Research Associated; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Teofarma; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: EMD Serono; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Tesaro; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Gentili; Speaker Bureau/Expert testimony: Fondazione Menarini; Speaker Bureau/Expert testimony: Menarini; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Noema S.r.l.; Speaker Bureau/Expert testimony: ACCMED; Speaker Bureau/Expert testimony: Dephaforum S.r.l.; Speaker Bureau/Expert testimony: Nadirex. P. Martin-Romano: Research grant/Funding (self), Non-remunerated activity/ies: AstraZeneca; Research grant/Funding (self), Non-remunerated activity/ies: Bristol Myers Squibb; Research grant/Funding (self), Non-remunerated activity/ies: Boehringer Ingelheim; Research grant/Funding (self): Janssen Cilag; Research grant/Funding (self), Non-remunerated activity/ies: Merck; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Roche; Research grant/Funding (self): Sanofi; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Johnson & Johnson; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: Medimmune; Non-remunerated activity/ies: NH TherA. E. Baudin: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Speaker Bureau/Expert testimony: AAA; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Hutchinson Pharma. J. Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. T. Sánchez-Pérez: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Genentech/Roche. M. Lamba: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer; Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company; Research grant/Funding (self), Shareholder/Stockholder/Stock options: Bristol-Myers Squibb. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. All other authors have declared no conflicts of interest.

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Proffered Paper - Developmental therapeutics Proffered Paper session

Invited Discussant 527O and 528O

Lecture Time
17:40 - 17:50
Speakers
  • Giulio Draetta (Houston, United States of America)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00
Proffered Paper - Developmental therapeutics Proffered Paper session

Q&A and live discussion

Lecture Time
17:50 - 18:00
Speakers
  • Christophe Massard (Villejuif, CEDEX, France)
Room
Channel 3
Date
20.09.2020
Time
16:20 - 18:00