Transgene S.A. announced that its Phase 2 study evaluating TG4001 in combination with avelumab (Bavencio) did not meet its primary objective of improving progression-free survival (PFS) in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors. The multi-center, open-label, randomized trial enrolled 100 patients who had disease progression after a maximum of one line of systemic treatment or were ineligible for first-line chemotherapy.
Efficacy Trend in Cervical Cancer Subgroup
Despite the overall negative result, a pre-planned subgroup analysis showed a positive efficacy trend in favor of the TG4001-containing regimen specifically in patients with cervical cancer, representing approximately half of the study population. This finding warrants further investigation, including analyses based on PD-L1 status, to confirm the potential benefit in this subgroup.
Safety and Tolerability
The combination of TG4001 and avelumab was well-tolerated, with adverse events consistent with previous observations, according to Transgene.
Mechanism of Action of TG4001
TG4001 (tipapkinogen sovacivec) is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA). It is engineered to express HPV16 antigens (E6 & E7) and includes human IL-2 as an adjuvant. The vaccine is designed to alert the immune system to cells presenting the HPV16 E6 and E7 antigens, commonly found in HPV16-related tumors, and to stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2).
Future Plans for TG4001
Transgene is currently evaluating the full study results in detail to determine the best way forward for the TG4001 program. The complete study results are expected to be presented at an upcoming scientific conference.
Dr. Alessandro Riva, Chairman and CEO of Transgene, stated, "Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favor of the combination regimen in cervical cancer patients. 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."
Focus on TG4050
Transgene remains focused on advancing its lead asset, TG4050, an individualized cancer vaccine for head and neck cancers. Additional data from the 24-month median follow-up of Phase 1 patients in the head and neck cancer trial are expected to be reported in November 2024 at the SITC conference. TG4050 is based on Transgene’s myvac platform, which generates personalized therapies based on patient-specific mutations (neoantigens) designed to induce a T-cell response to tumor cells.
