Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers.

Purpose: To evaluate tipapkinogene sovacivec (TG4001), a viral immunotherapeutic vaccine expressing human papillomavirus (HPV)16 E6/E7 non-oncogenic proteins and IL-2, in combination with avelumab in HPV16+ cancer patients.
Patients and Methods: In this open-label, phase Ib/II, multicenter study, HPV16+ advanced cancer patients received subcutaneous TG4001 at two dose levels (DL) in phase Ib and at the recommended phase II dose (RP2D) in phase II weekly for 6 weeks, then every 2 weeks (q2Wk) until 6 months, thereafter every 12 weeks, in combination with avelumab q2Wk starting from day 8. Exploratory end-points included immunomonitoring from sequential tumour and blood samples.
Results: Forty-three patients, mainly heavily pretreated (88% ≥ 1 previous line), were included in the safety analysis, with a majority of anal cancer (44%). No dose-limiting toxicities were reported, and DL2 (5 × 10 ⁷ Plaque forming units (PFU)) was selected as the RP2D. Treatment-related adverse events to TG4001 occurred in 93% of patients, mostly grade 1/2, with grade 3 anaemia in one patient and no grade 4/5. Overall response rate (ORR) was 22% (8/36) and 32% (8/25) in all and patients without liver metastases, respectively. Median progression-free survival (PFS) and Overall Survival (OS) were 2.8 months (95% CI: 1.4-5.6) and 11.0 months (95% CI:7.5-16.7) in the total population and 5.6 months (95% CI:1.6-9.6) and 13.3 months (95% CI:8.7-32.7) in patients without liver metastases. Antigen-specific T-cell response was identified in 7/11 patients by IFNγ ELISpot.
Conclusions: TG4001 in combination with avelumab is safe, demonstrated antitumour activity in heavily pre-treated HPV16+ cancer patients, and is currently being evaluated in a randomised phase II trial in patients with incurable anogenital cancer and limited hepatic involvement.
Gov Identifier: NCT03260023.
Competing Interests: Declaration of Competing Interest EB received honoraria from Eisai, MSD, Sandoz, Amgen; Meetings/travel grants and non-financial support from Daiichi Sankyo, Eisai, Amgen, Sandoz, MSD, Bristol-Myers Squibb, Novartis, Pfizer, Roche; has consulted for Egle Tx. CLT participated in advisory boards from MSD, BMS, Merck, Astra Zeneca, Celgene, Seattle Genetics, Roche, Novartis, Rakuten, Nanobiotix, and GSK. JPD participated in advisory boards for MSD, Roche, Genentech, BMS, Novartis, Merck, Pierre Fabre, MHCom, all of them to the benefit of his Institution and received research grant from Genentech, MSD, BMS, Astra Zeneca, Transgene, Amgen, all of them to the benefit of his Institution. PC received honoraria from ITeos Therapeutics, Amgen, Janssen, participated in advisory boards for OSE Immunotherapeutics, and Travel/accommodations support from Netris Pharma, Amgen, Merck, Roche, MSD, AstraZeneca. EP is co-founder of Egle Tx and has consulted for Transgene. MB, AT, HM, KB are employees of Transgene. The other authors declare no conflict of interest.
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