LBA2 - POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo)

Background

Inoperable locally recurrent/metastatic SCAC is associated with suboptimal PFS and OS, despite high initial response rates to platinum-based chemo. Retifanlimab, an anti–programmed cell death (PD)-1 monoclonal antibody, has shown antitumour activity in pts with advanced SCAC who progressed on platinum-based chemo (Rao S. ESMO Open. 2022;7:100529). POD1UM-303 evaluated the addition of retifanlimab to standard-of-care (SoC) chemo for previously untreated locally recurrent/metastatic SCAC.

Methods

This phase 3, double-blind, controlled trial enrolled treatment-naive pts aged ≥18 y with inoperable, locally recurrent/metastatic SCAC; (neo)adjuvant/radiosensitising chemo and well-controlled HIV infection were permitted. Pts were randomised 1:1 to 6 cycles of standard-dose C-P plus placebo (P arm) or retifanlimab 500 mg q4w (R arm) for up to 1 y with possibility of crossover. Primary endpoint was PFS by blinded independent central review per RECIST v1.1; secondary endpoints were OS (key endpoint), ORR, DCR, DOR, safety, and PK.

Results

As of 15 April 2024, 308 pts (R arm, 154; P arm, 154) were enrolled; median (range) age was 62 (29, 86) y, 72% of pts were female, 87% were White, 4% were known HIV-positive, and 36% had liver metastases. The trial met its primary endpoint. The median PFS was significantly higher in the R vs P arm (9.30 vs 7.39 mo; HR [95%CI], 0.63 [0.47, 0.84]; P=0.0006); a strong trend of improved OS was seen despite immature data (Table). Overall, addition of retifanlimab was tolerable, with no new safety signals to compromise or disrupt chemo administration. Table: LBA2

Efficacy by blinded independent central review of retifanlimab plusC-P vs placebo plus C-P in pts with SCAC

*Nominal P value.

Conclusions

This international study demonstrates encouraging efficacy and favourable benefit/risk ratio for retifanlimab plus SoC chemo as first-line treatment of locally recurrent/metastatic SCAC and suggests a new SoC.

Clinical trial identification

NCT04472429.

Editorial acknowledgement

Medical writing assistance was provided by Upasna Thapar, PhD, of Envision Pharma Group (Fairfield, CT, USA) and funded by Incyte Corporation.

Legal entity responsible for the study

Incyte Corporation, Wilmington, DE, USA.

Funding

Incyte Corporation, Wilmington, DE, USA.

Disclosure

S. Rao: Financial Interests, Personal, Advisory Board: Bayer, Hoopika, BeiGene, AstraZeneca, Merck Sernon, Seagen, Servier; Financial Interests, Personal, Invited Speaker: Bayer, Merck Sernon, Servier; Financial Interests, Personal, Other, Travel grants: Servier; Financial Interests, Personal, Expert Testimony: Boehringer. E. Samalin-Scalzi: Financial Interests, Personal, Advisory Board: Astellas, BeiGene, BMS, Pierre Fabre Oncology; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Pierre Fabre Oncology, Servier; Financial Interests, Personal, Other, Travel: Amgen, Merck, Serono, MSD, Pierre Fabre Oncology. L. Evesque: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Servier. M. Ben Abdelghani: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Merck, Serono; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Incyte, Merck, Pierre Fabre, Servier; Financial Interests, Personal, Other, Travel Grants: Roche. F. Morano: Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker Honoraria: Pierre-Fabre, Servier; Financial Interests, Personal, Other, Travel Grant: Amgen, Pierre-Fabre, Servier; Financial Interests, Institutional, Research Grant: Incyte. A.C. Roy: Financial Interests, Personal, Advisory Board: MSD, BMS, BeiGene, Takeda, Grey Wolf Therapeutics, Medison Pharma, AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Pierre Fabre, Limbic Oncology; Financial Interests, Personal, Member of Board of Directors: Southern Oncology SA Private Practice, Southern Oncology Clinical Research Unit; Financial Interests, Institutional, Research Grant: Merck, Specialised Therapeutics. L. Dahan: Financial Interests, Personal, Other, Honoraria: Amgen, BMS, Mylan, Oseus, Servier. M.P. Saunders: Financial Interests, Personal, Other, Honoraria: Amgen, Merck, Servier. R. Guimbaud: Financial Interests, Personal, Advisory Board: ADACAP, BMS; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pierre Fabre, Merck. A. Lievre: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications, Amgen, Bayer, BMS (Mexico), Incyte, Ipsen, Leo Pharma, Mylan, Novartis, Pierre Fabre, Roche, Servier, Viatris; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, Astellas Pharma, BMS (Mexico), Incyte, Pierre Fabre, Servier; Financial Interests, Institutional, Research Funding: Bayer, IntegraGen; Financial Interests, Personal, Other, Travel Grant: Boehringer Ingelheim, Ipsen, MSD Oncology, Mylan, Pierre Fabre, Roche, Servier. J. Maurel: Financial Interests, Personal, Advisory Role: Advance Medical, Cancer Expert Now, Delcath Systems, MSD; Financial Interests, Personal, Research Grant: Amgen, Guardant Health, Incyte, Merck, Terumo; Financial Interests, Personal, Other, Travel Grant: Amgen; Financial Interests, Personal, Non financial benefits, Leadership role: GEMCAD (Grupo Español Multidiciplinar en Cancer Digestivo). M. Fakih: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: AbbVie, Adagene, AstraZeneca, Bayer, BMS, Merck, Mirati, Pfizer, Taiho, Incyte; Financial Interests, Personal, Advisory Role: Eisai, Entos, Janssen, Nouscom, Roche/Genetech, Tempus. P. Zhang: Financial Interests, Personal, Stocks/Shares: Incyte; Financial Interests, Personal, Other, Employment: Incyte. J. Harrison: Financial Interests, Personal, Stocks/Shares: Incyte; Financial Interests, Personal, Other, Employment: Incyte. M. Jones: Financial Interests, Personal, Stocks/Shares: Incyte; Financial Interests, Personal, Other, Employment: Incyte. J. Spano: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Merck-MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Exact-Science, Gilead, Lilly, Novartis, Pierre Fabre Oncology, Pfizer, Roche; Financial Interests, Personal, Research Grant: MSD Avenir. P. Rochefort: Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Other, Travel Grant: Amgen, Sanofi, Servier. All other authors have declared no conflicts of interest.