2580 - Analysis of Tumor Hyperprogression (HP) With Nivolumab (Nivo) in Randomized, Placebo (Pbo)-Controlled Trials

Background

Tumor HP has been suggested to occur in some patients with solid tumors subsequent to PD-1/L1 inhibitor monotherapy; however, reports are based on nonrandomized, single-arm studies. Previous post-hoc analysis of HP with nivo was performed in the phase III ATTRACTION-2 trial, which randomized patients with gastric cancer who received ≥2 prior lines of therapy to nivo or pbo. Using the pbo arm as a surrogate for natural course of disease progression, nivo was not associated with HP at ≥ 20, ≥50, or ≥ 100% tumor growth rates. The current analysis expands this framework to assess HP in patients with extensive disease small cell lung cancer (ED SCLC) in the randomized, pbo-controlled CheckMate 451 trial.

Methods

CheckMate 451 was a phase III double-blind study that evaluated maintenance treatment in patients with ED SCLC without disease progression after platinum-based 1L chemotherapy. Patients were randomized to nivo 240 mg, nivo 1 mg/kg + ipilimumab 3 mg/kg, or pbo, within 9 weeks from the last dose of 1L chemotherapy (or ≤ 11 weeks for those receiving PCI or whole brain radiotherapy); HP analysis focused on the nivo (n = 280) and pbo (n = 275) arms. Tumor assessments occurred every 6 weeks for the first 36 weeks, then every 12 weeks until disease progression. HP was calculated as changes in size of the primary lesion (sum of longest diameters [SLD]), as assessed retrospectively among patients who had baseline and ≥1 on-treatment tumor measurement available (nivo, n = 177; pbo, n = 175).

Results

Baseline characteristics were balanced between treatment arms in the analysis population. Median increase in tumor size from baseline to first on-treatment assessment in the maintenance period was 2% with nivo vs 17% with pbo. Compared to the pbo arm, fewer patients on nivo had SLD increases of ≥20% (27% vs 46%), ≥50% (10% vs 22%), and ≥100% (3% vs 6%) at the first on-treatment scan.

Conclusions

In this analysis, nivo was not associated with HP in the pbo-controlled CheckMate 451 trial. These data are consistent with the previous analysis of ATTRACTION-2, suggesting that reports of HP with immunotherapy may reflect some patients’ natural course of disease.

Clinical trial identification

CheckMate 451 trial: NCT02538666.

ONO-4538-12/ATTRACTION-2 trial: NCT02267343.

Editorial acknowledgement

Stephen Gutkin and Jay Rathi, MA, of Spark Medica Inc, funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb and ONO Pharmaceutical Co. Ltd.

Funding

Bristol-Myers Squibb and ONO Pharmaceutical Co. Ltd.

Disclosure

M. Reck: Honoraria (self): AbbVie; Honoraria (self): Amgen ; Honoraria (self): AstraZeneca ; Honoraria (self): Boehringer Ingelheim; Honoraria (self): BMS ; Honoraria (self): Celgene; Honoraria (self): Lilly ; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche. Y. Feng: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. H.R. Kim: Honoraria (self), Advisory / Consultancy, Honoraria, consulting or advisory role: AstraZeneca; Honoraria (self), Advisory / Consultancy, Honoraria, consulting or advisory role: Roche; Honoraria (self), Advisory / Consultancy, Honoraria, consulting or advisory role: Boehringer Ingelheim. G. Plautz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. Y. Kang: Advisory / Consultancy: Ono ; Advisory / Consultancy: BMS; Advisory / Consultancy: Daehwa; Advisory / Consultancy: LSKBiopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MacroGenics ; Advisory / Consultancy: Zymeworks; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy: Astellas; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis. T.K. Owonikoko: Research grant / Funding (institution): Novartis, Astellas Pharma, Celgene, Bayer, Stemcentrx, Regeneron, AstraZeneca/MedImmune, AbbVie, G1 Therapeutics, Bristol-Myers Squibb, Corvus Pharmaceuticals, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea BioTherapeutics, Incyte, Merck; Advisory / Consultancy: Novartis, Celgene, Lilly, Sandoz, AbbVie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Heron Pharmaceutical, ARMO Bi; Shareholder / Stockholder / Stock options, Co-founder: Cambium Oncology. P. Nghiem: Honoraria (self), Honoraria for consulting: EMD Serono-Pfizer, Merck, Regeneron-Sanofi; Research grant / Funding (institution): EMD Serono, Bristol-Myers Squibb. J. Sheng: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb.