1528P - A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors

Background

Despite therapeutic developments for patients with advanced HER2+ solid tumors, significant unmet medical needs still exist. The T-cell antigen coupler (TAC) technology is an approach to modifying T-cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T-cell receptor. TAC T-cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-HER2 is an autologous T-cell product comprising T-cells expressing HER2 TAC.

Methods

The ongoing clinical trial (NCT04727151) is evaluating the safety and preliminary anti-tumor activity of TAC01-HER2 treatment of HER2+ solid tumors. Subjects undergo leukapheresis followed by lymphodepletion chemotherapy (LDC) prior to TAC01-HER2 infusion. In phase I dose escalation, TAC01-HER2 is administered at increasing doses (Cohorts 1-4) in adult subjects after ≥2 lines of therapy. Dose limiting toxicities (DLT) are assessed up to 28 days from TAC01-HER2 infusion. In phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors.

Results

As of 23 April 2023, 19 patients with solid tumors have been treated in Cohorts 1-4. Three were HER2 1+ or 2+/FISH-. One DLT event of grade (G) 3 pneumonitis has been reported in 1 subject in Cohort 4. No neurotoxicity has been reported. Most subjects treated at Cohorts 3-4 experienced CRS which resolved with supportive therapy. Thirteen subjects have reported a total of 26 serious adverse events, with 1 G3 pneumonitis, 1 G1, 3 G2 and 1 G3 CRS related to TAC01-HER2. A 67% disease control rate (DCR) was observed in Cohorts 2-4 at 4 weeks restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 83%. Two patients had an unconfirmed partial response (uPR). At Cohort 4, a uPR was observed in a subject with GEJ (HER2 2+, FISH+) with 100% reduction of target lesion. This patient had progressed on 4 prior lines of therapy including trastzumab and trastuzumab deruxtecan.

Conclusions

Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. Dose escalation is complete.

Clinical trial identification

NCT04727151.

Editorial acknowledgement

Legal entity responsible for the study

Triumvira Immunologics.

Funding

Triumvira Immunologics.

Disclosure

D. Olson: Financial Interests, Personal, Advisory Board: Novartis, Alphasights, GLG Consulting, MJH Life Sciences; Financial Interests, Institutional, Local PI: Takeda, Astellas, Adaptimmune, Instil Bio, Inhibrix; Non-Financial Interests, Principal Investigator: CTRL Therapeutics. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd., Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, BOLT Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: Bolt Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. M. George: Financial Interests, Personal, Advisory Board: Seattle Genetics, OBI Pharma; Financial Interests, Institutional, Research Grant: Incyte, Oncolytics. S. Saibil: Financial Interests, Personal, Advisory Board: Janssen, Novartis, Sanofi Genzyme. A. Giordano: Financial Interests, Personal, Advisory Board: Pfizer. E. Lichtenstein: Financial Interests, Institutional, Full or part-time Employment: Rutgers Cancer Institute of NJ. M. Apostolopoulou; D. Kirkwood; S. Dang: Financial Interests, Personal, Full or part-time Employment: Triumvira. K. Moss: Financial Interests, Institutional, Full or part-time Employment: Triumvira Immunologics, Inc.; Financial Interests, Personal, Stocks/Shares: Triumvira Immunologics, Inc. D. Adib: Financial Interests, Institutional, Officer: Triumvira; Financial Interests, Institutional, Stocks/Shares: Triumvira; Financial Interests, Institutional, Trial Chair: Triumvira. All other authors have declared no conflicts of interest.