LBA42 - POD1UM-202: Phase II study of retifanlimab in patients (pts) with squamous carcinoma of the anal canal (SCAC) who progressed following platinum-based chemotherapy

Background

Effective salvage treatment for advanced SCAC has not been established; however, checkpoint immunotherapy shows promise. Retifanlimab (INCMGA00012), a humanized IgG4 monoclonal antibody that recognizes human programmed cell death protein 1 (PD-1), has demonstrated activity and tolerability across a broad range of solid tumors. POD1UM-202 was designed to evaluate retifanlimab in pts with previously treated advanced SCAC.

Methods

Phase II, single-arm study in pts 18 years or older with progression following standard therapy and RECIST measurable disease. Prior immunotherapy was not allowed. Pts with well-controlled human immunodeficiency virus (HIV) infection were eligible. Retifanlimab was administered intravenously at 500 mg every 4 weeks. The primary study endpoint was overall response rate (ORR) assessed by independent central review (ICR) per RECIST v1.1.

Results

94 pts were enrolled with median age of 64 years, most were female (64.9%) and white (76.6%), and had an ECOG PS of 0 (41.5%) or 1 (58.5%). 73.4% had received prior CRT, 17% RT alone, and 97% had received platinum. Liver metastasis was reported in 39 (41.5%) pts and 9 (9.6%) were known to be HIV-positive. Median (range) duration of follow-up was 7 (<1–19) months. ICR confirmed responses were reported in 13 (13.8%) pts (1 complete response; 12 partial responses) and 33 (35.1%) pts had stable disease; median (range) DOR was 9.5 (5.6–not estimable) months. Responses were observed regardless of PD-L1 expression, liver metastases, or HIV-positive status. Median (95% CI) PFS and OS were 2.3 (1.9–3.6) and 10.1 (7.9–NE) months, respectively. Responses were associated with marked prolongation of PFS and OS. Retifanlimab was well-tolerated, including in the HIV-positive population, with a safety profile as expected for a PD-1 inhibitor and a low incidence of treatment discontinuation due to immune-related adverse events (2.1%).

Conclusions

Results from this large phase 2 trial demonstrate encouraging efficacy and an acceptable safety profile with retifanlimab in pts with previously treated advanced or metastatic SCAC, including pts with well-controlled HIV infection.

Clinical trial identification

NCT03597295 (July 24, 2018); EudraCT: 2018-002070-51 (2018-11-14).

Editorial acknowledgement

Editorial assistance was provided by Kakuri Omari of Envision Pharma Group (Philadelphia, PA, USA).

Legal entity responsible for the study

Incyte Corporation.

Funding

Incyte Corporation.

Disclosure

S. Rao: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy, Non-remunerated activity/ies: Bayer; Honoraria (institution), Advisory/Consultancy, Non-remunerated activity/ies: Celgene; Honoraria (institution), Advisory/Consultancy: Shire; Non-remunerated activity/ies: Incyte. J. Capdevila: Advisory/Consultancy, Research grant/Funding (institution): Advanced Accelerator Applications; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Sanofi. S. Kim: Research grant/Funding (institution): Bioproject Pharma; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Servier; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Ipsen; Honoraria (institution), Advisory/Consultancy: MSD. L. Dahan: Honoraria (institution): Amgen; Honoraria (institution): Sanofi; Honoraria (institution): Servier. M. Fakih: Advisory/Consultancy: Taiho; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Speaker Bureau/Expert testimony: Guardant; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis. L.H. Jensen: Research grant/Funding (institution): 2cureX; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MSD. K-L.G. Spindler: Honoraria (institution), Non-remunerated activity/ies: Amgen; Honoraria (institution), Non-remunerated activity/ies: Merck Serono; Honoraria (institution), Non-remunerated activity/ies: Nordic Drugs BV; Honoraria (institution), Non-remunerated activity/ies: Roche/Genentech. D. Arnold: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy: Terumo; Advisory/Consultancy: Biocompatibles; Advisory/Consultancy: Helsinn Therapeutics; Advisory/Consultancy: Roche; Research grant/Funding (institution): Sanofi. M. Cornfeld: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. M. Jones: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. C. Tian: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. M. Catlett: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. J-P. Spano: Honoraria (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy: Biogaran; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Gilead Sciences; Honoraria (institution): Leo Pharma; Honoraria (institution): Lilly; Honoraria (institution): Mylan; Honoraria (institution): Myriad Genetics; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Pierre Fabre; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.