TG4001 Plus Avelumab Fails to Boost PFS in Recurrent/Metastatic, HPV16+ Cervical, Anogenital Tumors

The addition of TG4001 (tipakinogene sovacivec) to avelumab (Bavencio) did not lead to an improvement in progression-free survival (PFS) compared with avelumab alone in patients with recurrent or metastatic, human papillomavirus 16 (HPV16)–positive cervical or anogenital tumors, missing the primary end point of a phase 2 trial (NCT03260023).¹

A preplanned subgroup analysis of the study demonstrated a positive efficacy trend favoring the combination of TG4001 and avelumab in patients with cervical cancer, who accounted for approximately half of the patients enrolled in the study. Transgene, the developer of TG4001, said in a news release that additional analyses are needed to evaluate the efficacy of the combination within this subgroup.

Regarding safety, the combination was well tolerated, and adverse effects were consistent with prior data.

“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. 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,” Alessandro Riva, chairman and chief executive officer of Transgene, stated in a news release.

TG4001 is a viral immunotherapeutic vaccine that expresses the non-oncogenic HPV proteins E6 and E7, as well as interleukin-2. The vaccine is intended to provide the E6 and E7 proteins in an inflammatory context to provoke an adaptive immune response toward cancer cells that express E6 and E7.²

The phase 1b/2 trial enrolled patients at least 18 years of age with histologically or cytologically documented metastatic or refractory/recurrent cervical, vulvar, vaginal, penile, or anal cancer that was HPV16 positive and not amenable to curative surgical resection or curative radiotherapy with documented disease progression.³ Patients were required to have an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; at least 1 measurable lesion per RECIST 1.1 criteria; and adequate hematological, hepatic, and renal function. Patients with baseline liver metastases needed to have limited hepatic disease.

No more than 1 prior systemic therapy in the recurrent or metastatic setting was permitted. Prior systemic therapy for recurrent or metastatic disease was not required for patients who experienced recurrence or progression within 6 months of completing multimodal therapy for localized or locally advanced disease; those who were unsuitable for platinum-based chemotherapy; and patients who refused chemotherapy or other standard therapies for metastatic or recurrent disease.

During part 2 of phase 2, patients were randomly assigned to received TG4001 in combination with avelumab or avelumab alone.

Along with the primary end point of PFS per RECIST 1.1 criteria in part 2 of phase 2, secondary end points included overall response rate per RECIST 1.1 criteria, overall survival, duration of response, disease control rate, and safety.

“We would like to thank all the patients and caregivers who have taken part in this study for their important contribution,” Riva added in the news release.1 “With a diversified portfolio of novel immunotherapies targeting solid tumors, our strategy remains focused on advancing our lead asset, TG4050, an individualized cancer vaccine for head and neck cancers for use following surgery and adjuvant therapy. We expect to report additional data on TG4050 from the 24-month median follow-up of phase 1 patients in our head and neck cancer trial in November 2024 at the SITC [Annual Meeting].”

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 22, 2024. https://www.transgene.fr/wp-content/uploads/20241014_TG4001_Phase_II_update_EN.pdf
2. Borcoman E, Lalanne A, Delord JP, et al. Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers. Eur J Cancer. 2023;191:112981. doi:10.1016/j.ejca.2023.112981
3. Phase Ib/​II of TG4001 and avelumab in HPV16 positive R/​M cancers. ClinicalTrials.gov. Updated April 3, 2024. Accessed October 22, 2024. https://clinicaltrials.gov/study/NCT03260023