1037O - MASTERKEY-265: A phase III, randomized, placebo (Pbo)-controlled study of talimogene laherparepvec (T) plus pembrolizumab (P) for unresectable stage IIIB–IVM1c melanoma (MEL)

Background

In the phase Ib part of MASTERKEY-265, T + P showed promising complete response rate (CRR) of 33% in 21 patients (pts) with advanced MEL. Here we report efficacy and safety from the phase III, randomized, double-blind MASTERKEY-265/KEYNOTE-034 study of T + P vs Pbo + P in pts with stage IIIB–IVM1c MEL (NCT02263508).

Methods

Unresectable stage IIIB-IVM1c, anti-PD-1 naïve, MEL pts with injectable lesions were randomized 1:1 to T + P or Pbo + P. T was given at ≤ 4 x 10⁶ PFU followed by ≤ 4 x 10⁸ PFU 3 weeks later and Q2W until dose 5, and Q3W thereafter. P was given IV 200 mg Q3W. Dual primary endpoints were progression-free survival (PFS) per mRECIST 1.1 by blinded independent central review and overall survival (OS). Secondary endpoints included objective response rate (ORR), complete response rate (CRR), durable response rate (DRR), duration of response (DOR), and safety. Results reported here are the primary PFS and interim OS analyses (data cutoff [DCO] PFS Mar 2, 2020; OS Sep 29, 2020).

Results

A total of 692 pts were randomized (346 to T + P, 346 to Pbo + P); as of the OS DCO, all pts were off study treatment (tx). Median follow-up was 31.0 mo (range: 0.3, 53.0). 6.9% had stage IVM1c disease, 32.7% had LDH > ULN, and 64.9% had PD-L1+ status. Median PFS was 14.3 mo (range: 10.3, 22.1) for the T + P arm and 8.5 mo (range: 5.7, 13.5) for the Pbo + P arm (HR 0.86, 95% CI 0.71, 1.04, P = 0.13). Median OS was not reached for the T + P arm and 49.2 mo (range: 40.6, NE) for the Pbo + P arm (HR 0.96, 95% CI 0.76, 1.24, P = 0.74). OS was not expected to achieve statistical significance at the primary OS analysis. ORR was 48.6% for the T + P arm (CRR 17.9%) and 41.3% for the Pbo + P arm (CRR 11.6%). DRR was 42.2% in the T + P arm and 34.1% for the Pbo + P arm. There was no difference in DOR between arms (P = 0.87, HR [95% CI] 1.04 [0.67, 1.60]). Gr 3+ TEAEs occurred in 161 (46.7%) pts receiving T + P and in 151 (44.0%) pts receiving Pbo + P. Gr 3+ tx-related AEs (TRAEs) occurred in 73 (21.2%) pts receiving T + P and in 55 (16%) pts receiving Pbo + P.

Conclusions

T + P did not significantly improve PFS or OS vs Pbo + P. There was a 5.8 mo numeric difference in PFS between arms. Safety results of T + P were acceptable and consistent with the known safety profiles of each agent.

Clinical trial identification

NCT02263508.

Editorial acknowledgement

Medical writing support was provided by Christopher Nosala, PhD (Amgen Inc.).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc., Merck & Co.

Disclosure

A. Ribas: Financial Interests, Personal, Other, Honoraria: Amgen Inc.; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Chugai; Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Vedanta; Financial Interests, Personal, Advisory Board: Advaxis; Financial Interests, Personal, Advisory Board: Apricity; Financial Interests, Personal, Advisory Board: Arcus; Financial Interests, Personal, Advisory Board: Compugen; Financial Interests, Personal, Advisory Board: CytomX; Financial Interests, Personal, Advisory Board: Five Prime; Financial Interests, Personal, Advisory Board: Highlight; Financial Interests, Personal, Advisory Board: ImaginAb; Financial Interests, Personal, Advisory Board: Isoplexis; Financial Interests, Personal, Advisory Board: Kalthera; Financial Interests, Personal, Advisory Board: Kite-Gilead; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Advisory Board: PACT; Financial Interests, Personal, Advisory Board: Pharma; Financial Interests, Personal, Advisory Board: RAPT; Financial Interests, Personal, Advisory Board: Rgenix; Financial Interests, Personal, Advisory Board: Tango; Financial Interests, Institutional, Research Grant: Agilent; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Advaxis; Financial Interests, Personal, Stocks/Shares: Apricity; Financial Interests, Personal, Stocks/Shares: Arcus; Financial Interests, Personal, Stocks/Shares: Compugen; Financial Interests, Personal, Stocks/Shares: CytomX; Financial Interests, Personal, Stocks/Shares: Five Prime; Financial Interests, Personal, Stocks/Shares: Highlight; Financial Interests, Personal, Stocks/Shares: ImaginAb; Financial Interests, Personal, Stocks/Shares: Isoplexis; Financial Interests, Personal, Stocks/Shares: Kalthera; Financial Interests, Personal, Stocks/Shares: Kite-Gilead; Financial Interests, Personal, Stocks/Shares: Merus; Financial Interests, Personal, Stocks/Shares: PACT; Financial Interests, Personal, Stocks/Shares: Pharma; Financial Interests, Personal, Stocks/Shares: RAPT; Financial Interests, Personal, Stocks/Shares: Rgenix; Financial Interests, Personal, Stocks/Shares: Tango. J. Chesney: Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: Replimune; Financial Interests, Personal, Other, Travel: Amgen Inc.; Financial Interests, Personal, Other, Travel: Replimune; Financial Interests, Institutional, Research Grant: Amgen Inc.; Financial Interests, Institutional, Research Grant: Replimune; Financial Interests, Institutional, Research Grant: Lovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: MedImmune. G.V. Long: Financial Interests, Personal, Advisory Role: Aduro Biotech; Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: Array Biopharma Inc.; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim International GmbH; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Hexel AG; Financial Interests, Personal, Advisory Role: Highlight Therapeutics S.L.; Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: Novartis Pharma AG; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: QBiotics Group Limited; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Role: SkylineDX B.V.; Financial Interests, Personal, Advisory Role: Specialised Therapeutics Australia Pty Ltd.. J.M. Kirkwood: Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Checkmate Pharmaceuticals; Financial Interests, Personal, Advisory Role: Harbour BioMed; Financial Interests, Personal, Advisory Role: Iovance Biotherapeutics; Financial Interests, Personal, Advisory Role: Istari Oncology; Financial Interests, Personal, Advisory Role: OncoSec Medical Inc.; Financial Interests, Personal, Advisory Board: Novartis Pharmaceuticals; Financial Interests, Personal, Advisory Role: Scopus BioPharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Elsevier; Financial Interests, Personal, Advisory Role: OncoCyte Corporation; Financial Interests, Personal, Advisory Role: Millenium Pharmaceuticals/Takeda Pharmaceutical; Financial Interests, Personal, Advisory Role: Axio Research/Instil Bio; Financial Interests, Personal, Advisory Role: Immunocore LLC; Financial Interests, Personal, Advisory Role: Natera Inc.; Financial Interests, Personal, Advisory Role, Amgen Inc.: DermTech; Financial Interests, Institutional, Research Grant: Amgen Inc.; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Castle Biosciences, Inc.; Financial Interests, Institutional, Research Grant: Checkmate Pharmaceuticals; Financial Interests, Institutional, Research Grant: Immunocore LLC; Financial Interests, Institutional, Research Grant: Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis Pharmaceuticals. R. Dummer: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role, Amgen Inc.: Roche; Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sun Pharma; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Catalym. I. Puzanov: Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: 4SC. C. Hoeller: Financial Interests, Personal, Advisory Role: Amgen Inc.; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Inzyte; Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Amgen Inc.; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp and Dohme; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Roche. T.F. Gajewski: Financial Interests, Personal, Stocks/Shares: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares: Evelo Therapeutics; Financial Interests, Personal, Stocks/Shares: Five Prime; Financial Interests, Personal, Stocks/Shares: Pyxis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Jounce Therapeutics; Financial Interests, Personal, Advisory Role: Adaptimmune; Financial Interests, Personal, Advisory Role: FOGPharma; Financial Interests, Personal, Advisory Role: Allogene Therapeutics; Financial Interests, Personal, Advisory Role: Pyxis; Financial Interests, Personal, Advisory Role: Trillium Therapeutics; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Gilead Sciences; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: Ono Pharmaceutical; Financial Interests, Institutional, Funding: Aduro Biotech; Financial Interests, Institutional, Funding: Pyxis; Financial Interests, Institutional, Funding: Bayer. R. Gutzmer: Non-Financial Interests, Personal, Other, Travel: Roche; Non-Financial Interests, Personal, Other, Travel: Bristol-Myers Squibb; Non-Financial Interests, Personal, Other, Travel: SUN; Non-Financial Interests, Personal, Other, Travel: Merck-Serono; Non-Financial Interests, Personal, Other, Travel: Pierre Fabre; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Amgen Inc.; Financial Interests, Institutional, Research Grant: Merck-Serono; Financial Interests, Institutional, Research Grant: SUN Pharma; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Almirall Hermal; Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Board: Amgen Inc.; Financial Interests, Personal, Advisory Board: SUN Pharma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Merck-Serono; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Merck Sharp and Dohme; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Amgen Inc.; Financial Interests, Institutional, Funding: Merck-Serono; Financial Interests, Institutional, Funding: SUN Pharma; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Pierre-Fabre; Financial Interests, Institutional, Funding: Philogen; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Amgen Inc.; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Invited Speaker: Almirall Hermal; Financial Interests, Personal, Invited Speaker: SUN Pharma; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Pierre-Fabre. P. Rutkowski: Financial Interests, Personal, Advisory Board: Blueprint Medicines; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Pfizer. L. Demidov: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Honoraria: Merck Sharp and Dome; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche. P.F. Ferrucci: Financial Interests, Personal, Expert Testimony: Bristol-Myers Squibb; Financial Interests, Personal, Expert Testimony: Merck Sharp and Dohme; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: Pierre Fabre; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb. S.J. Diede: Financial Interests, Personal, Full or part-time Employment: Merck & Co.; Financial Interests, Personal, Stocks/Shares: Merck & Co.. J.R. Anderson: Financial Interests, Personal, Full or part-time Employment: Merck & Co.; Financial Interests, Personal, Stocks/Shares: Merck & Co.. S. Treichel: Financial Interests, Personal, Stocks/Shares: Amgen Inc.; Financial Interests, Personal, Full or part-time Employment: Amgen Inc.. E. Chan: Financial Interests, Personal, Stocks/Shares: Amgen Inc.; Financial Interests, Personal, Full or part-time Employment: Amgen Inc.. F..S. Hodi: Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Board: Surface; Financial Interests, Personal, Advisory Board: Compass Therapeutics; Financial Interests, Personal, Advisory Board: Apricity; Financial Interests, Personal, Advisory Role: Aduro; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Pionyr; Financial Interests, Personal, Advisory Board: Torque; Financial Interests, Personal, Advisory Board: Bicara; Financial Interests, Personal, Advisory Role: Pieris Pharmaceutical; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Board: Checkpoint Therapeutics; Financial Interests, Personal, Advisory Role: Idera; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Board: Bioentre; Financial Interests, Personal, Advisory Role: Gossamer; Financial Interests, Personal, Advisory Role: Phio; Financial Interests, Personal, Advisory Board: Iovance; Financial Interests, Personal, Advisory Board: Trillium; Financial Interests, Personal, Advisory Role: Catalym. H.J. Gogas: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Amgen Inc.: Pierre Fabre; Financial Interests, Institutional, Funding: Amgen Inc.; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Merck Sharp and Dohme; Financial Interests, Institutional, Research Grant: Pfizer. All other authors have declared no conflicts of interest.