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- Ian Chau (Sutton, United Kingdom)
- Hanneke W. Van Laarhoven (Amsterdam, Netherlands)
1203O - FOLFOX plus nivolumab and ipilimumab versus FOLFOX induction followed by nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Results from the randomized phase II Moonlight trial of the AIO
- Sylvie Lorenzen (Munich, Germany)
Abstract
Background
FOLFOX plus nivolumab (nivo) has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas. To reduce toxicity, there is a need to evaluate if short-term induction chemotherapy followed by immunotherapy as an alternating treatment is as effective, while more tolerable. The aim of this second part of the Moonlight trial was to evaluate if mFOLFOX induction therapy followed by nivo plus ipilimumab (ipi) is less toxic but equally effective compared to both regimens combined together. Results of the other study parts will be presented elsewhere.
Methods
The AIO-STO-0417 trial (Moonlight) is a four-arm investigator-initiated trial, whereof two arms (A1/A2) are presented here. Pts were randomized 1:2 to FOLFOX plus nivo 240 mg; q2w and ipi 1 mg/kg; q6w administered in parallel (arm A1; parallel treatment) or three cycles of mFOLFOX induction treatment followed by nivo and ipi (arm A2; sequential treatment). PD-L1 expression was centrally assessed. Primary endpoint was progression-free survival at 6 months (PFS@6), main secondary endpoints were OS, PFS, objective response rate (ORR) and safety.
Results
Ninety patients were randomized (30 pts to arm A1 and 60 pts to A2). Baseline characteristics were: median age 62y, GEJ, 51%, intestinal type, 33%. Forty-one percent had PD-L1 CPS≥1 (available in 74% of pts). Pts received a median of 11 cycles in A1 vs 7 cycles in A2. Adverse events of grade ≥3 were seen in 93% of the pts for arm A1 and 73% for arm A2, serious adverse events (SAE) in 70% in arm A1 and 62% in A2. Median follow-up was 7.3 mo. PFS@6 was 57% in arm A1 vs 28% in A2 (p=.012) with median PFS 8.4 vs 4.0 mo, respectively (p=.006). Median OS was not yet reached in A1 vs 9.1 mo in A2, ORR was 47% vs 30%, respectively. The results were similar in the PD-L1+ group.
Conclusions
FOLFOX chemotherapy plus nivolumab and ipilimumab administered in parallel was clearly more effective than FOLFOX induction followed by nivo and ipi. Although associated with lower toxicity, our study doesn’t support the use of sequential treatment in the first-line setting.
Clinical trial identification
EudraCT-No. 2017-002080-18 NCT03647969.
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest.
Funding
Bristol-Myers Squibb.
Disclosure
P.C. Thuss-Patience: Financial Interests, Personal, Advisory Board: Novartis, MSD, Bristol-Myers Squibb, Merck Serono, Roche, Astellas Pharma, Servier, Daiichi Sankyo, Pfizer, Lilly; Financial Interests, Institutional, Research Grant: Novartis, Merck Serono. G. Folprecht: Financial Interests, Personal, Advisory Board: Bayer, BMS, Exact Sciences, Merck, MSD, Pierre Fabre, Roche / Genentech, Sanofi-Aventis, Servier; Financial Interests, Personal, Invited Speaker: Falk Foundation, Lilly, Roche / Genentech. E. Goekkurt: Financial Interests, Personal, Advisory Board: MSD, Bristol-Myers Squibb, Roche, Sanofi . T.J. Ettrich: Financial Interests, Personal, Advisory Board: Eisai, MSD, Bayer, Roche, Sanofi, Bristol-Myers Squibb, Celgene, Incyte, AstraZeneca, Merck Serono, Pierre Fabre, Servier, Lilly, Ipsen; Financial Interests, Personal, Other: Ipsen; Financial Interests, Personal, Research Grant: Baxalta/Shire . D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, PharmaMar, Roche; Financial Interests, Institutional, Principal Investigator: BMS, EUSA-Pharma, Lilly, PharmaMar, Roche; Financial Interests, Institutional, Project Lead: Novartis; Non-Financial Interests, Personal, Member: ASCO, Connective Tissue Oncology Society (CTOS), Deutsche Krebsgesellschaft - German Cancer Society (DKG), Deutsche Sarkomstiftung (DSS). T.O. Götze: Financial Interests, Personal, Advisory Board: Lilly, MSD Oncology, Bayer, SERVIER, Roche, Novartis, Incyte, Foundation Medicine, Bristol-Myers Squibb ; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Research Grant: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss, Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte. S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, Merck Sharp & Dohme, MacroGenics; Financial Interests, Personal, Advisory Role: Astra/Daichii ; Financial Interests, Personal, Speaker’s Bureau: Lilly, AIO gGmbH, Bristol-Myers Squibb, MCI Group ; Financial Interests, Personal, Ownership Interest: Institut für Klinische Krebsforschung GmbH ; Financial Interests, Personal, Research Grant: Celgene, Lilly, Medac, Hospira, Sanofi, German Cancer Aid, German Research Foundation, Federal Ministry of Education and Research, Roche, Vifor Pharma, Eurozyto, Immutep, Ipsen, Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca. All other authors have declared no conflicts of interest.
Invited Discussant 1203O
- Ian Chau (Sutton, United Kingdom)
Q&A
LBA60 - Evaluation of gemcitabine and paclitaxel versus gemcitabine alone after FOLFIRINOX failure or intolerance in metastatic pancreatic ductal adenocarcinoma: Results of the randomized phase III PRODIGE 65 - UCGI 36 - GEMPAX UNICANCER study
- Christelle De la Fouchardiere (Lyon, France)
Abstract
Background
No clinical trial has evaluated the benefit of 2d-line chemotherapy in metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) after FOLFIRINOX (FFX) failure.
Methods
In this randomized phase 3 trial, pts were assigned in a 2:1 ratio to either receive GEMPAX (gemcitabine 1000mg/m2 + paclitaxel 80mg/m2 IV infusion at D1, 8 and 15 every 28 days) (arm A/experimental) or GEM (gemcitabine alone) (arm B/control) regimen after failure or intolerance to 1st-line FFX regimen. Primary endpoint was overall survival (OS). Secondary endpoints included Progression-Free Survival (PFS), Objective Response Rate (ORR) and safety.
Results
From June 2019 to March 2021, 211 pts were randomised (140 in arm A/71 in arm B) in 31 French centers. Median age was 64 years (30-86), 62% were male, ECOG-PS 0-1 88%. Tumor location in the pancreas was head (33%) tail (25%) or body (22%). 76% pts were metastatic at diagnosis. Median follow-up was 6.3
Conclusions
The combination of paclitaxel + gem brought no benefit in OS over gem alone to mPDAC pts in 2nd-line setting but significantly improved both PFS and ORR. Imbalance in 3rd line therapies and notably the use of taxanes in gem monotherapy arm might explain the lack of benefit in OS. Altogether, these results highlight the medical need for new therapeutic options for pre-treated mPDAC pts.
Clinical trial identification
NCT03943667 EudraCT: 2018-002886-21.
Legal entity responsible for the study
UNICANCER.
Funding
INCa (Institut National du Cancer).
Disclosure
C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol-Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai; Financial Interests, Institutional, Invited Speaker: Pierre Fabre Oncologie, Servier. D. Malka: Financial Interests, Personal, Expert Testimony: AbbVie; Financial Interests, Personal, Advisory Board: Agios, Amgen, AstraZeneca, BMS, Bayer, HalioDx, Incyte, MSD, Merck Serono, Pierre Fabre Oncologie, Roche, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Bayer, Foundation Medicine, HalioDx, Incyte, Leo Pharma, MSD, Medscape, Merck Serono, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Viatris, Veracyte; Other, Other, Travel expenses for medical congresses: Amgen, Bayer, BMS, Merck Serono, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Viatris. J. Raimbourg: Financial Interests, Personal, Invited Speaker, Travel reimbursement: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, Amgen, Sanofi; Financial Interests, Personal, Other, invited speaker and travel reimbursement: Pierre Fabre. D. Botsen: Non-Financial Interests, Personal, Other, non-financial support: GSK, Novartis, Roche, Servier, Amgen; Financial Interests, Personal, Other, personal fees: Pierre Fabre; Financial Interests, Personal, Invited Speaker, personal fees: Chugai. M. Jary: Financial Interests, Personal, Invited Speaker: pierre fabre, servier, incyte; Other, Other, participation to congresses: pierre fabre; Other, Other, Participation to congresses: roche, bayer. J. Bachet: Financial Interests, Personal, Other, honoraria and consulting: AMGEN, MSD, Pierre Fabre, Servier; Financial Interests, Personal, Other, honoraria, consulting and research grant: AstraZeneca; Financial Interests, Personal, Other, honoraria, consulting and travel reimbursement: Bayer, Merck Serono; Financial Interests, Personal, Other, honoraria and travel reimbursement: Roche, Sanofi; Financial Interests, Personal, Other, honoraria: VIATRIS; Financial Interests, Personal, Advisory Role: Incyte. C. Neuzillet: Financial Interests, Personal, Advisory Role: Servier, Amgen, Novartis, Incyte, Nutricia, Baxter; Financial Interests, Personal, Other, consulting, principal investigator: AstraZeneca, BMS; Financial Interests, Personal, Other, consulting, congresses reimbursement: Merck, MSD, Mylan; Financial Interests, Personal, Other, congresses reimbursement, principal investigator: Ose Immunotherapeutics; Financial Interests, Personal and Institutional, Other, congresses reimbursement and funding (institutional): Roche. N. Williet: Financial Interests, Personal, Advisory Role: Accord Healthcare, Mayoly, Viatris; Financial Interests, Personal, Other, consulting and travel reimbursement: Servier; Financial Interests, Personal, Other, travel reimbursement: Ipsen, MSD. O. Bouche: Financial Interests, Personal, Other, honoraria: Amgen, Apmonia Therapeutics, Bayer, Merck, Pierre Fabre, Roche, Sanofi, Servier. F. Ghiringhelli: Financial Interests, Personal and Institutional, Other, honoraria, consulting, research grant (institutional), travel reimbursement: Roche; Financial Interests, Personal, Other, honoraria, research grant (institutional), travel reimbursement: AstraZeneca; Financial Interests, Personal, Other, honoraria: Merck Serono, BMS, MSD, Bayer; Financial Interests, Personal, Other, honoraria and travel reimbursement: Amgen; Financial Interests, Personal, Invited Speaker, honoraria and travel reimbursement: Servier. All other authors have declared no conflicts of interest.
Invited Discussant LAB60
- Hanneke Wilmink (Amsterdam, Netherlands)
Q&A
LBA12 - Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients (pts) with an FGFR2-fusion or rearrangement (f/r), FGFR inhibitor (FGFRi)-naïve cholangiocarcinoma (CCA): ReFocus trial
- Antoine Hollebecque (Villejuif, Cedex, France)
Abstract
Background
Previous, nonselective FGFRi have validated FGFR2 f/r as a target in CCA by achieving an objective response rate (ORR) of ∼20-40% with duration of response (DOR) ∼5-9 months. However, off-target toxicity and emergence of polyclonal FGFR2 resistance limit their efficacy. RLY-4008 is the first highly selective, potent FGFR2 inhibitor designed to target both driver alterations and FGFR resistance mutations. Here we present the initial efficacy of RLY-4008 in pts with a FGFR2 f/r, FGFRi-naïve CCA.
Methods
ReFocus (RLY-4008-101), a Phase 1/2 study (NCT04526106), enrolled pts with advanced solid tumors who received RLY-4008 orally (20-200 mg QD or BID). FGFR2 f/r status was determined by local testing. Key objectives were investigator-assessed ORR per RECIST v1.1, DOR, and safety. Safety was analyzed in all dosed pts and efficacy in pts with FGFR2 f/r, FGFRi-naïve CCA with measurable disease and an opportunity for ≥2 tumor assessments to confirm response.
Results
As of 01AUG22, 38 pts with FGFR2 f/r, FGFRi naïve CCA were efficacy evaluable. Most pts received the recommended phase 2 dose (RP2D); most (68%) remain on treatment with median duration of 6 months (<0.1 - 18.5 months). Potent efficacy was observed across all doses, particularly at the RP2D with an ORR of 88% (Table). One pt treated at the RP2D had a near-complete response and subsequent tumor resection with curative intent. DOR is not yet mature, with majority of responses ongoing. Across all doses (N=195), the most common treatment-related AEs (TRAEs) were low-grade stomatitis (48%), PPE (46%), and dry mouth (31%). No grade 4/5 TRAEs were observed.
RP2D (70 mg QD) All dose levels 15 (88.2 [63.6 - 98.5]) 24 (63.2 [46.0 - 78.2]) Confirmed ORR, n (% [95% CI]) 14 (82.4 [56.6 - 96.2]) 22 (57.9 [40.8 - 73.7]) Response ongoing, n/N (%) 15/15 (100.0) 19/24 (79.2) 17 (100.0) 36 (94.7) Remain on treatment, n (%) 15 (88.2) 26 (68.4)
Conclusions
RLY-4008 is a promising next-generation inhibitor with potential to transform the treatment of FGFR2 f/r, FGFRi-naïve CCA. Pivotal testing continues in ReFocus.
Clinical trial identification
NCT04526106.
Legal entity responsible for the study
Relay Therapeutics.
Funding
Relay Therapeutics.
Disclosure
A. Hollebecque: Financial Interests, Personal, Advisory Board: Amgen, BMS, Bailea, Incyte, Servier, QED Therapeutics, Tahio, Relay Therapeutics. M. Borad: Financial Interests, Institutional, Funding: Relay Therapeutics. L. Goyal: Financial Interests, Personal, Advisory Role: Alentis Therapeutics, Genentech, Exelixis, Incyte, QED Therapeutics, Servier, Sirtex, Taiho, Alentis, Black Diamond, H3Biomedicine, Transthera, Kinnate; Financial Interests, Institutional, Funding: Adaptimmune, Bayer, Eisai, Merck, Macrogenics, Genentech, Novartis, Incyte, Eli Lilly, Loxo Oncology, Relay Therapeutics, QED Therapeutics, Servier, Taiho, LEAP Therapeutics, BMS, Nucana. A. Schram: Financial Interests, Institutional, Funding: Relay Therapeutics, AstraZeneca, ArQule, BeiGene/Springworks, Black Diamond Therapeutics, Elevation Oncology, Kura, Lilly, Merus, Northern Biologics, Pfizer, PMV Pharma, Repare Therapeutics, Revolution Medicine, Surface Oncology; Financial Interests, Personal, Advisory Board: Relay Therapeutics, Mersana. J.O. Park: Non-Financial Interests, Personal, Other: BMS/Celgene, Servier; Financial Interests, Personal, Other: MedPacto, ABL Bio; Financial Interests, Personal, Advisory Role: AstraZeneca, Servier, MedPacto. P.A. Cassier: Financial Interests, Personal, Invited Speaker: ITeos, Amgen, Janssen; Financial Interests, Personal, Advisory Role: OSE Immunotherapeutics; Financial Interests, Institutional, Funding: Bayer, GSK, Janssen, Lilly, AstraZeneca, Roche/Genentech, Merck Serono, Toray Industries, Novartis, Plexxikon, BMS, Taiho Pharmaceutical, Transgene, Innate Pharma, Loxo, Blueprint Medicines, Celgene, AbbVie, Merck Sharp & Dohme; Financial Interests, Personal, Netris Pharma, Amgen, Merck Sharp & Dohme, AstraZeneca/MedImmune. S.D. Kamath: Financial Interests, Personal, Advisory Board: Exelixis, Guardant Health, Tempus. D.T. Wai Meng: Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Advisory Role: Novartis, Celgene, Sirtex, MSD, Eisai, Ipsen, Bayer, BMS; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, BMS, Roche; Financial Interests, Personal, Other: AstraZeneca. E. Dotan: Non-Financial Interests, Personal, Other: Relay Therapeutics; Financial Interests, Institutional, Funding: Lilly, Pfizer, Incyte, AstraZeneca, SMP Oncology, Zymeworks, NGM Biopharmaceuticals, Ipsen, Syneos Health; Financial Interests, Personal, Advisory Role: QED, Taiho, Helsinn, Incyte, Basilea, SMP Oncology, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Pfizer. R. Kim: Financial Interests, Personal, Advisory Role: Bayer, Elelixis, Lilly, QED Therapeutics, Servier, Taiho Oncology; Financial Interests, Personal, Speaker’s Bureau: Incyte, LIlly; Financial Interests, Institutional, Funding: Bayer, BMS, Eisai. D. Oh: Financial Interests, Institutional, Funding: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA. C. Liao: Financial Interests, Personal, Advisory Board: Incyte, Transthera, QED Therapeutics. M. Millward: Financial Interests, Institutional, Funding: Relay Therapeutics; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, The Limbic, Roche, BMS, Takeda Pharmaceuticals, Guardant Health, BeiGene, Amgen Australia, Merck, Lilly Australia; Financial Interests, Personal, Invited Speaker: BMS, Roche, The Limbic; Financial Interests, Personal, Other, travel: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Leadership Role: Melanoma & Skin Cancer Trials Australia. C. Ferté: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics. R. Blakesley: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Full or part-time Employment: Relay Therapeutics. B. Wolf: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Leadership Role: Relay Therapeutics; Financial Interests, Personal, Full or part-time Employment: Relay Therapeutics. V. Subbiah: Financial Interests, Institutional, Funding: Relay Therapeutics. R.K. Kelley: Financial Interests, Institutional, Advisory Role: Exelixis, Agios, AstraZeneca, Ipsen; Financial Interests, Personal, Advisory Role: Genentech/Roche, Kinnate, Exact Sciences; Financial Interests, Institutional, Funding: Bayer, BMS, Agios, AstraZeneca, Eli Lilly, EMD Serono, Ipsen, Loxo Oncology, MSD, QED Therapeutics, Partner Therapeutics, Relay Therapeutics, Surface Oncology. All other authors have declared no conflicts of interest.
Invited Discussant LBA12
- Chiara Braconi (Glasgow, United Kingdom)