Abstract 882TiP
Background
Nivolumab (NIVO), a programmed death-1 immune checkpoint inhibitor, is approved globally as an effective treatment across multiple cancer types. Several studies are investigating subcutaneous (SC) NIVO, co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), as it may benefit patients, clinicians, and the healthcare system. Patients with cancer often prefer SC over IV administration. SC dosing may alleviate the need for IV vein ports, lower the risk of dosing errors, allow more patient flexibility, and reduce dose preparation and administration times, thereby optimizing occupancy in infusion centres. In CheckMate 8KX, SC NIVO + rHuPH20 was well tolerated in patients with different solid tumours and exposures were comparable to IV NIVO 3 mg/kg Q2W (from historical data). Investigations of SC NIVO vs IV NIVO in patients with clear cell renal cell carcinoma (phase 3 CheckMate 67T study) or melanoma following complete resection are ongoing.
Trial design
CheckMate 6GE is a multicentre, randomized, open-label, phase 3 study evaluating the pharmacokinetic (PK) noninferiority of SC NIVO + rHuPH20 vs IV NIVO in patients with melanoma following complete resection. Inclusion criteria are stage IIIA/B/C/D or stage IV melanoma, complete resection ≤ 12 weeks before randomization or treatment assignment, and ECOG performance status ≤ 1. Key exclusion criteria include a history of uveal/mucosal melanoma, untreated/unresected CNS metastases, concurrent malignancy or history of prior malignancy active ≤ 2 years before randomization or treatment assignment, known or suspected autoimmune disease, serious/uncontrolled medical disorder 4 weeks before screening, and prior immunotherapy. Patients (N ≈ 286) are randomized (1:1) to receive SC NIVO or IV NIVO in part 1 (stratified by stage [IIIA/B vs IIIC/D/IV] and weight [< 80 kg vs ≥ 80 kg]) or enrolled in the part 2 PK cohort. PK, safety, efficacy, immunogenicity, and cancer treatment satisfaction will be evaluated (Table). Table: 882TiP
| Primary endpoints |
| Time-averaged NIVO serum concentration over the first 28 days |
| Cmin at steady state |
| Secondary endpoints |
| Safety and tolerability, eg, AEs, serious AEs, immune-mediated AEs, death, administration-related reactions, laboratory abnormalities |
| Recurrence-free survival |
| Overall survival |
| Additional PK parameters: Cmin on Day 28, Cmax after the first dose, time to Cmax after the first dose, Cmax at steady state, time-averaged NIVO serum concentration at steady state |
| Immunogenicity (anti-NIVO and neutralizing antibodies) |
| Cancer Treatment Satisfaction Questionnaire |
AE, adverse event; Cmax, maximum NIVO serum concentration; Cmin, minimum NIVO serum concentration.
Clinical trial identification
NCT05297565.
Editorial acknowledgement
Professional medical writing and editorial assistance was provided by George Hsu, PhD, and Matthew Weddig, BA, of Spark Medica Inc., funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. P. Mohr: Financial Interests, Other, Grants and personal fees: Bristol Myers Squibb, MSD; Financial Interests, Other, personal fees: Pierre Fabre, GSK, Novartis, Sanofi, Roche, Merk Germany. R. Dronca: Financial Interests, Invited Speaker, Honoraria: Elsevier, Eisai, EMD Serono, Genzyme, Immunovaccine Technologies, Natera, Regeneron Pharmaceuticals, Sanofi Genzyme. M. Wilson: Financial Interests, Personal, Invited Speaker, Honoraria: Eisai , Pfizer. B. Gurm: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Howansky: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. W. Ng: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Ravimohan: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. H. Vezina: Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb ; Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. M. Pe Benito: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. P. Gurman: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. All other authors have declared no conflicts of interest.