T-VEC is the first FDA-approved oncolytic immunotherapy designed to activate antitumor immune responses. Pembro is a mAb against human programmed death receptor-1 that can stimulate inactivated anticancer T cells and is approved for the treatment (tx) of SCCHN. This combination of agents may further enhance antitumor immune response. This phase 1b/3 study will evaluate the safety and efficacy of T-VEC and pembro in patients (pts) with R/M SCCHN progressing after platinum (NCT02626000).
The primary objective for phase 1b is to assess dose-limiting toxicities (DLTs). Key secondary objectives include objective response rate, best overall response, and safety. Key eligibility criteria include histologically confirmed R/M SCCHN unsuitable for resection/radiotherapy, progressing after platinum tx, and injectable lesions. T-VEC was given by intralesional injection ≤ 8 mL of 106 PFU/mL on day 1, then after 3 w, ≤ 8 mL of 108 PFU/mL Q3W; pembro was given IV at 200 mg Q3W. Approximately 18 pts in the safety cohort and an additional 22 pts for long-term safety and efficacy will be enrolled into phase 1b.
28 pts have been enrolled; 16 are DLT evaluable: 12 (75%) male, median age 57.5 y (range: 35, 77), ECOG 1 (75%). There was a DLT in 1 pt after 2 doses of both drugs: fatal arterial hemorrhage (AH). Grade 3/4 AEs were seen in 6 (38%) of pts - none led to tx discontinuation. There were 2 grade 5 AEs: AH (DLT) and disease progression. Incidence of SAEs possibly related to T-VEC was 5 (31.3%: chills, pyrexia, stridor, odynophagia, AH) and to pembro was 2 (12.5%: eczema, pyrexia) - none led to tx discontinuation.Table:
|All DLT Evaluable* (N = 16)||Non-DLT Evaluable (N = 12)||All Pts (N = 28)|
|All tx-emergent AEs||15 (93.8)||11 (91.7)||26 (92.9)|
|Grade 3||5 (31.2)||2 (16.7)||7 (25)|
|Grade 4||1 (6.3)||1 (8.3)||2 (7.1)|
|Grade 5||2 (12.5)||7 (58.3)||9 (32.1)|
|AEs related to T-VEC||11 (68.8)||2 (16.7)||13 (46.4)|
|Grade 3||4 (25)||1 (8.3)||5 (17.9)|
|Grade 4||0 (0)||0 (0)||0 (0)|
|AEs related to pembro||9 (56.3)||1 (8.3)||10 (35.7)|
|Grade 3||1 (6.3)||1 (8.3)||2 (7.1)|
|Grade 4||0 (0)||0 (0)||0 (0)|
To be DLT evaluable, pt must have had ≥ 6 w of follow up from the initial dosing and have received ≥ 2 doses of T-VEC and pembro in combination, or have a DLT during the DLT evaluation period after at least 1 dose of T-VEC and pembro.
There was 1 DLT of 16 evaluable pts. The combination regimen was deemed safe to continue into the phase 1b efficacy portion. The protocol was amended to exclude pts who have received reirradiation to the neck and are at high risk for AH.
Clinical trial identification
Legal entity responsible for the study
Amgen Inc. and Merck
K. Harrington: Corporate-sponsored research from AstraZeneca, Merck Sharp Dohme; Consulting fees from Amgen, AstraZeneca, Bristol-Myers Squib, Merck, Merck Sharp Dohme, Pfizer; Speakers Bureau from Amgen, AstraZeneca, Bristol-Myers Squib, Merck, Merck Sharp Dohme. S. Treichel, J.J. Kim: Employee and stock shareholder of Amgen Inc. J. Cheng: Employee and stock shareholder of Merck. J. Chesney: Consulting fees from Amgen Inc. All other authors have declared no conflicts of interest.