Tracon’s subcutaneous hopes evaporate

This week’s collapse in the shares of the micro-cap Tracon Pharmaceuticals reflects the group’s chances of becoming a player in the subcutaneous PD-(L)1 space. Tracon has US rights to envafolimab, a subcutaneous anti-PD-L1 MAb, under a 2020 deal with China’s Alphamab Oncology, and this relates specifically to soft tissue sarcoma, a niche indication in which no anti-PD-(L)1 drugs are approved. A US sarcoma filing hinged on the phase 2 Tracon-sponsored Envasarc trial, but according to a curious announcement on Wednesday this appears doomed. Tracon says Envasarc cleared an earlier futility boundary, and an independent data-review committee recommended that the trial continue. However, among an extra 27 patients versus December’s update there have been no further responses, and the resulting 5.5% ORR is short of Tracon’s hurdle of 11%; even 11% ORR was, according to Jones Research, “not sufficient for successful market adoption”, given that Keytruda, and Opdivo plus Yervoy, generated 23% and 29% respectively in trials not pursued to filing. It’s a separate question why envafolimab underperformed in this way; presumably the issue is baseline characteristics or hitting PD-L1 rather than PD-1, and not envafolimab’s SC delivery. In China envafolimab is approved for MSI-H/MMRd tumours. Envasarc's progressDec 2020Envasarc starts: envafolimab +/- Yervoy in undifferentiated pleomorphic sarcoma or myxofibrosarcomaOct 2022IDMC recommendation to continue based on safety review from 12 patientsDec 2022IDMC recommendation to continue based on efficacy review from 36 patientsJun 2023Envafolimab + Yervoy cohort is discontinued (lack of efficacy vs envafolimab)Sep 2023Envasarc clears IDMC’s futility threshold of 6.5% ORRDec 2023Interim ORR by BICR said to be 8.7% (4/46)Apr 2024Final ORR by BICR said to be 5.5% (4/73), missing primary endpoint hurdle of 11%Source: OncologyPipeline.