5630 - Efficacy and safety of nivolumab (Nivo) + ipilimumab (Ipi) in patients (pts) with recurrent/metastatic (R/M) cervical cancer: Results from CheckMate 358

Background

High unmet medical need persists in pts with R/M cervical cancer; median overall survival (OS) is < 17 mo after 1L therapy with few options in 2L. Per current guidelines, pts whose tumors express programmed death ligand 1 (PD-L1) are eligible for pembrolizumab in the 2L setting. CheckMate 358 (NCT02488759) is an ongoing open-label, multi-cohort, phase I/II study of Nivo +/- Ipi in virus-associated cancers regardless of PD-L1 expression. Here we report an interim analysis of pts with R/M cervical cancer, with or without prior systemic therapies (PST), receiving Nivo + Ipi.

Methods

Eligible pts had R/M cervical cancer treated with 0-2 PST. Pts were randomized to Nivo 3mg/kg Q2W + Ipi 1mg/kg Q6W (Combo A), or Nivo 1mg/kg + Ipi 3mg/kg Q3W for 4 doses followed by Nivo 240mg Q2W (Combo B), for ≤24 mo until progression or unacceptable toxicity. Primary endpoint: investigator-assessed objective response rate (ORR) by RECIST 1.1; secondary endpoints: OS, progression-free survival (PFS) and duration of response.

Results

Median follow-up was 10.7 mo [Combo A, n = 45] and 13.9 mo [Combo B, n = 46]. ORR was higher in Combo B vs Combo A without PST (46% vs 32%) and with PST (36% vs 23%; Table). Median PFS in Combo A was 13.8 mo (95% CI 2.1, not reached [NR]) in pts without PST and 3.6 mo (1.9, 5.1) in pts with PST. Median PFS in Combo B was 8.5 mo (3.7, NR) without PST and 5.8 mo (3.5, 17.2) with PST. Median OS in Combo A was NR (17.4, NR) in pts without PST and 10.3 mo (7.9, 15.2) in pts with PST. Median OS in Combo B was NR without PST (13.9, NR) and 25.4 mo with PST (17.5, NR). Incidence of all/grade 3–4 treatment-related adverse events (AEs) was 80.0%/28.9% in Combo A and 82.6%/37.0% in Combo B. No new safety signals were identified.Table:

LBA62

Measured by tumor proportion score

Defined as the proportion of treated pts with a best overall response of confirmed complete response, partial response or stable disease

Conclusions

These results suggest clinical benefit from two regimens of Nivo + Ipi in pts with R/M cervical cancer regardless of PD-L1 status. Combo B had notable efficacy in pts with PST. AEs were manageable and consistent with previous reports of Nivo + Ipi therapy.

Clinical trial identification

NCT02488759.

Editorial acknowledgement

Writing and editorial assistance was provided by Brooke Middlebrook of Evidence Scientific Solutions Inc, and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb, Princeton, NJ, USA.

Funding

Bristol-Myers Squibb, Princeton, NJ, USA.

Disclosure

R.W. Naumann: Research grant / Funding (institution): Bristol-Myers Squib; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Advisory / Consultancy, Research grant / Funding (institution): SutroBio. A. Oaknin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO: Pharma Mar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO & VHIR: Clovis Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), grant for VHIO: Immunogen; Advisory / Consultancy: Genmab; Research grant / Funding (institution), VHIR: Abbie Deutchland; Research grant / Funding (institution), VHIO: Ability Pharmaceuticals; Research grant / Funding (institution), VHIO: Advaxis Inc; Research grant / Funding (institution), VHIR: Aeterna Zentaris; Research grant / Funding (institution), VHIR: Amgen SA; Research grant / Funding (institution), VHIO: Aprea Therapeutics AB; Research grant / Funding (institution), VHIO: Eisai Ltd; Research grant / Funding (institution), VHIO: F. Hoffmann - La Roche Ltd. ; Research grant / Funding (institution), VHIO: Regeneron Pharmaceuticals; Research grant / Funding (institution), VHIO: Merck Sharp & Dohme de España SA; Research grant / Funding (institution), VHIO: Millennium Pharmaceuticals Inc.. T. Meyer: Advisory / Consultancy: Beigene; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): BTG; Advisory / Consultancy: Eisai; Advisory / Consultancy: Ipsen; Research grant / Funding (institution): Bayer; Travel / Accommodation / Expenses, consultancy: BMS. C. Lao: Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Research grant / Funding (self): Genentech; Research grant / Funding (self): Merck; Research grant / Funding (self): Dynavax; Research grant / Funding (self): Novartis; Advisory / Consultancy: Immunocore. Y. Bang: Advisory / Consultancy: Hanmi; Advisory / Consultancy, Research grant / Funding (institution): Genexine; Advisory / Consultancy: Samyang Biopharm; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy: Taiho; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Taiho; Research grant / Funding (institution), Ono, CKD Pharma, Genexine Grant to Institution.: Takeda. V. Boni: Advisory / Consultancy: Loxo therapuetics; Advisory / Consultancy: Ideaya. W.H. Sharfman: Research grant / Funding (institution), personal fees: BMS; Research grant / Funding (institution), personal fees: Merck; Research grant / Funding (institution), personal fees: Novartis; Advisory / Consultancy: Iovance; Advisory / Consultancy: Regeneron. K. Harano: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Chugai; Advisory / Consultancy: Eizai; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.H. Chung: Honoraria (self), Received honorarium for ad hoc scientific advisory board participation: Bristol-Myers Squibb. S.L. Topalian: Shareholder / Stockholder / Stock options, Licensing / Royalties: Aduro Biotech; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Compugen; Advisory / Consultancy, Shareholder / Stockholder / Stock options: DNAtrix; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Dragonfly Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: ERVAXX; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Five Prime Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: FLX Bio; Shareholder / Stockholder / Stock options: Jounce Therapeutics; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Potenza Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tizona Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: WindMIL; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Dynavax; Advisory / Consultancy, Licensing / Royalties: lmmunomic Therapeutics; Advisory / Consultancy: Janssen Oncology; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses, Licensing / Royalties: Bristol-Myers Squibb. T. Chen: Licensing / Royalties: Combination therapy with anti-IL-8 antibodies and anti-PD-1 antibodies for treating cancer. B. Li: Full/Part-time employment: Bristol-Myers Squibb. A.M. Barrows: Full / Part-time employment: Bristol-Myers Squibb. A. Horvath: Full / Part-time employment: Bristol-Myer Squibb. K.N. Moore: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Tesaro; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Onco Med; Advisory / Consultancy: Samumed; Research grant / Funding (self), Research grant / Funding (institution): Lilly; Advisory / Consultancy: Eisai. All other authors have declared no conflicts of interest.