LBA39 - Final 5-year results of the phase II, multicenter, randomized, open-label trial of talimogene laherparepvec (T-VEC) neoadjuvant treatment (Tx) plus surgery vs immediate surgery in patients (pts) with resectable stage IIIB-IVM1a melanoma (MEL)

Background

The risk of recurrence after resection remains high for pts with advanced MEL. Neoadjuvant therapies before surgery shrink tumors, reduce recurrence risks, and potentially improve long-term outcomes. T-VEC, an intralesional oncolytic viral immunotherapy, selectively replicates in MELs and enhances the antitumor immune response. The primary analysis (NCT02211131) reported a 2-y recurrence-free survival (RFS) of 29.5% for T-VEC + surgery and 16.5% for surgery alone (overall HR 0.75; 80% CI 0.58-0.96) in pts with resectable stage IIIB-IVM1a MEL, persisting at 3 y (overall HR 0.74; 80% CI 0.57-0.95) (Dummer Nat Med 2021). Here, we report the final 5-y analysis.

Methods

Pts with resectable stage IIIB-IVM1a MEL and ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions were randomized 1:1 to six doses of neoadjuvant T-VEC, then surgery (Arm 1) or immediate surgery alone (Arm 2). T-VEC was administered at standard doses until surgery, no remaining injectable tumors, or intolerance. The investigator’s choice adjuvant Tx was allowed and used similarly in both arms. The final RFS was analyzed 5 y after randomization.

Results

As of May 30, 2022, the median follow-up for all 150 pts was 63.3 mo (range 0.1-86.8). For Arm 1 vs Arm 2, the 5-y KM estimates of RFS were 22.3% and 15.2% (HR 0.76, 80% CI 0.60-0.97), the 5-y KM estimates of EFS were 43.7% and 27.4% (HR 0.57, 80% CI 0.43-0.76), and the 5-y KM estimates of OS were 77.3% and 62.7% (HR 0.54, 80% CI 0.36-0.81). HRs for local RFS, regional RFS, and distant metastases-free survival (DMFS) were 0.82 (80% CI 0.64-1.06), 0.81 (80% CI 0.62-1.05), and 0.73 (80% CI 0.57-0.94), respectively. No new safety signals were detected.

Conclusions

In the final readout of the largest randomized trial of neoadjuvant Tx in pts with resectable stage IIIB-IVM1a MEL, we report durable improvements in RFS, EFS, DMFS, and OS at 5 y with neoadjuvant T-VEC + surgery vs standard surgery. These results provide proof of concept that an intratumorally administered oncolytic agent can elicit a meaningful long-term systemic effect and support the use of neoadjuvant T-VEC + surgery in this pt population.

Clinical trial identification

NCT02211131.

Editorial acknowledgement

Medical writing support was provided by Christopher Nosala, PhD (Amgen Inc.) and Shubha Dastidar, PhD (Cactus Life Sciences, part of Cactus Communications) and was funded by Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

R. Dummer: Financial Interests, Personal, Advisory Role, has intermittent, project-focused consulting and/or advisory relationships outside of the submitted work: Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm. D. Gyorki: Financial Interests, Personal, Funding, Travel: Amgen; Financial Interests, Personal, Other, Honoraria: Amgen, Bristol Myers Squibb, Novartis. J. Hyngstrom: Financial Interests, Personal, Funding, Travel: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Nektar. A. Berger: Financial Interests, Personal, Speaker’s Bureau: Cardinal Health. R. Conry: Financial Interests, Personal, Speaker’s Bureau: Merck, Bristol Myers Squibb, Amgen Inc, Novartis, Array, Regeneron-Sanofi. L. Demidov: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Other, Consulting fees: MSD, Bristol Myers Squibb, Novartis, Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Honoraria: MSD, Roche; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb, Novartis. L. Ning: Financial Interests, Personal, Full or part-time Employment: Parexel. T. Lawrence: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. M. Faries: Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting: Merck, Instil Bio. M. Ross: Financial Interests, Personal, Other, Honoraria: Merck, Amgen Inc; Financial Interests, Personal, Advisory Board: Amgen Inc, Merck; Financial Interests, Personal, Research Grant: Amgen Inc, Provectus; Financial Interests, Personal, Funding, Travel funding: Amgen Inc, Merck, Provectus, Novartis, Castle Biosciences.