959O - Gavocabtagene autoleucel (gavo-cel, TC-210) dose escalation in refractory mesothelin-expressing solid tumors

Background

The safety and activity of gavo-cel is being evaluated in a dose-escalation study in patients (pts) with refractory ovarian cancer, malignant mesothelioma (MPM), cholangiocarcinoma (ChoCa), or non-small cell lung cancer.

Methods

Dose escalation follows a 3+3 design. Autologous T-cells were transduced with a T-cell receptor fusion construct (TRuC™) encoding an anti-MSLN single domain antibody fused to the CD3ε subunit. The TRuC then integrates into native TCRs, allowing HLA-independent T-cell engagement to MSLN on cancer cells. Eligibility required central confirmation of 2+ or 3+ MSLN expression by IHC in ≥50% of tumor cells.

Results

As of April 28th, 2021, 17 pts (12 MPM, 4 ovarian, 1 ChoCa) had received a single IV dose of gavo-cel at 5x10⁷/m² either alone (dose level [DL] 0, n=1) or after lymphodepletion (LD) (DL1, n=6), at 1x10⁸/m² either alone (DL2, n=1) or after LD (DL3, n=5), or at 5x10⁸/m² either alone (DL4, n=1) or after LD (DL5, n=3). Median number of prior therapies was 5 (range, 2-9, immune checkpoint inhibitors 65%, anti-MSLN agents 33%). Bridging therapy was required by 53% of pts. Twelve pts were evaluable for safety and efficacy. One DLT (gr3 pneumonitis at DL1) and 2 gr3 CRS events were reported, both resolving with tocilizumab/corticosteroids. Median target lesion regression was 24% (range 5-75%). DCR was 92%. Two pts with ICI-refractory MPM and 1 with TP53-mutated platinum-resistant ovarian cancer had a PR (ORR 25%), including 1 MPM with a complete metabolic response by PET. After a median follow-up of 7 months, the median PFS was 6 months and the median OS was 13 months. Gavo-cel contained a median of 30.45% naïve transduced T-cells (range, 14.1-56.2). Peak expansion occurred on day 15 (median, 854 copies/μg DNA) at DL1 and on day 7 (median, 10,824 copies/μg DNA) at DL3. No differences in cytokine levels were seen between pts treated at DL1 and DL3. A decrease in soluble MSLN related peptides (median -42.56%) and serum megakaryocyte potentiating factor levels (median -38.57%) was observed post infusion among pts with detectable baseline levels.

Conclusions

The toxicity profile of gavo-cel was manageable. Activity was observed among pts with refractory MSLN-expressing solid tumors. Dose escalation is ongoing to determine the RP2D.

Clinical trial identification

NCT03907852.

Editorial acknowledgement

Legal entity responsible for the study

TCR2 Therapeutics.

Funding

TCR2 Therapeutics.

Disclosure

D.S. Hong: Financial Interests, Institutional, Principal Investigator: TCR2 Therapeutics. S.L. SciMentum: Financial Interests, Institutional, Principal Investigator: TCR2 Therapeutics. J. Tanyi: Financial Interests, Institutional, Principal Investigator: TCR2 Therapeutics. L. MacMullen: Financial Interests, Personal, Full or part-time Employment: TCR2 Therapeutics. L. Jalbert: Financial Interests, Personal, Full or part-time Employment: TCR2 Therapeutics. V.P. Muzithras: Financial Interests, Personal, Full or part-time Employment: TCR2 Therapeutics. K. Zikaras: Financial Interests, Personal, Full or part-time Employment: TCR2 Therapeutics. R.E. O’Cearbhaill: Financial Interests, Institutional, Principal Investigator: TCR2 Therapeutics. A. Quintás-Cardama: Financial Interests, Personal, Full or part-time Employment: TCR2 Therapeutics. R. Hassan: Financial Interests, Institutional, Principal Investigator: TCR2 Therapeutics. All other authors have declared no conflicts of interest.