Cancer Vaccine Combo Does Not Improve PFS in Cervical/Anogenital Tumors

Developers designed TG4001 based on a non-propagative, highly attenuated Vaccinia vector that expresses HPV16 antigens and adjuvant interleukin-2.

Combining the investigational therapeutic vaccine TG4001 (tipapkinogen sovacivec) with avelumab (Bavencio) did not improve progression-free survival (PFS) compared with avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors, according to findings from a phase 2 trial (NCT03260023).¹

The TG4001-based combination did not meet the trial’s primary end point of PFS. Based on a preplanned subgroup analysis, investigators identified a positive efficacy trend favoring the TG4001 arm among those with cervical cancer, although confirmation via further evaluation based on factors such as PD-L1 status was needed. Approximately half of the study population consisted of those with cervical cancer.

Data showed that treatment with TG4001 plus avelumab was well tolerated among patients. The toxicity profile of this treatment was comparable with prior reports.

Transgene, the developer of TG4001, stated in a press release that it plans to thoroughly assess the full trial results to determine suitable next steps for their program.

“Failure to meet the primary objective in our phase 2 study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favor of the combination regimen in [patients with] cervical cancer,” Alessandro Riva, MD, chairman and chief executive officer at Transgene, stated in the press release.¹ “We plan to complete a full and rigorous analysis of the data before deciding on any path forward for this asset, in particular in cervical cancer, in the context of the evolving treatment landscape. The complete study results will be presented at an upcoming scientific conference.”

Developers designed TG4001 based on a non-propagative, highly attenuated Vaccinia vector that expresses HPV16 antigens and adjuvant interleukin-2 (IL-2). Investigators hypothesize that the vaccine works by alerting the immune system to cells expressing HPV16 antigens associated with HPV16-related disease and stimulating infection-clearing activity by via IL-2.

Investigators of the multicenter, open-label, randomized phase 2 trial aimed to evaluate the efficacy of TG4001 in combination with avelumab vs avelumab monotherapy among patients with metastatic or recurrent HPV16-positive cervical and anogenital cancers following progression on a prior line of systemic therapy.

The trial’s primary end points included the safety and tolerability of TG4001 plus avelumab in the phase 1b portion, overall response rate per RECIST v1.1 criteria in part 1 of the phase 2 portion, and PFS based on RECIST v1.1 criteria in part 2 of the phase 2 portion of the trial.² Secondary end points included overall survival, duration of response, and disease control rate.

Patients 18 years and older with an ECOG performance status of 0 or 1, a minimum life expectancy of 3 months, and histologically or cytologically confirmed metastatic or recurrent HPV-16 positive cervical, vulvar, vaginal, penile, or anal cancer were eligible for enrollment on the trial. Additional requirements for study entry included having disease not amenable to curative surgical resection or radiotherapy with documented disease progression, limited hepatic disease for those with liver metastases at baseline, availability of tumor tissue via biopsy, and 1 or more measurable lesions per RECIST v1.1 guidelines. Having adequate hematological, hepatic, and renal function was also required to enroll.

Those with prior exposure to immunotherapy, chronic treatment with systemic corticosteroids or other immunosuppressive drugs for at least 4 weeks, or central nervous system metastases that were not clinically stable were not eligible for enrollment on the trial. Having other active malignancies requiring concurrent systemic intervention or any prior organ transplantation including allogeneic stem cell transplantation was also grounds for exclusion from the trial.

References

1. Transgene provides update on phase II trial of therapeutic cancer vaccine TG4001 in recurrent or metastatic HPV16-positive cervical and anogenital cancers. News release. Transgene. October 14, 2024. Accessed October 15, 2024. https://tinyurl.com/2kx6z43e
2. Phase Ib/​II of TG4001 and avelumab in HPV16 positive R/​M cancers. ClinicalTrials.gov. Updated April 3, 2024. Accessed October 14, 2024. https://tinyurl.com/2es6ax83