Treatment with gavocabtagen-autoleucel demonstrated efficacy and tolerability in patients with mesothelin-expressing solid tumors, according to updated data from an ongoing Phase 1/2 clinical trial.
The anti-mesothelin cell therapy Gavocabtagene Autoleucel (Gavo-Cel) significantly improved clinical outcomes in patients with advanced mesothelin-expressing solid tumors, according to data from the Phase 1 portion of a clinical trial outlined in a recent press release from TCR became2 therapeutics.
These data are from an ongoing phase 1/2 study (NCT03907852) of Gavo-cel in patients with malignant pleural/peritoneal mesothelioma (MPM), non-small cell lung cancer (NSCLC), ovarian cancer or cholangiocarcinoma. Treatment with Gavo-Cel resulted in a disease control rate, defined as response or sustained stable disease for at least 3 months post-infusion, of 77% in 30 evaluable patients with MPM, ovarian cancer or cholangiocarcinoma. Tumor regression (range 4% to 80%) occurred in 93% of patients as measured by blinded independent central review (BICR). Target lesion regression greater than 30% occurred in 8 patients, of whom 6-4 with mesothelioma and 2 with ovarian cancer achieved partial responses by RECIST v1.1 criteria. In addition, the overall response rate (ORR) after BICR was 29% and 21% in patients with ovarian cancer and MPM, respectively. Median progression-free survival (PFS) was 5.8 months and median overall survival (OS) was 8.1 months in patients with ovarian cancer and 5.6 months and 11.2 months in patients with MPM, respectively.
“Results from the Phase 1 study underscore the potential clinical value of Gavo-Cel in a very heavily pretreated patient population who are receiving our engineered T cells on average as a sixth line of therapy,” Alfonso Quintás-Cardama, MD, Chief Medical Officer of the TCR2 Therapeutics, according to a press release. “These results clearly support the further development of Gavo-Cel in the Phase 2 portion of the study, where we believe the combination with checkpoint inhibitors and the ability to re-treat patients with additional doses of Gavo-Cel will enable us will allow patient exposure to Gavo-Cel to be increased, potentially leading to even higher response rates and improved durability of benefit.”
Gavo-cel is a T cell receptor fusion construct targeting the cell surface glycoprotein mesothelin, overexpression of which is associated with poorer prognosis in some solid tumors including ovarian cancer, MPM and cholangiocarcinoma.
The Phase 1 portion of this study evaluated 30 patients who received 4 escalating doses of Gavo-Cel as part of a modified 3+3 design. Treatment was tested at each escalating dose in 2 separate dose levels: first without lymphodepletion and then after lymphodepletion. In the upcoming Phase 2 portion of this study, 75 patients in an MPM cohort and 20 patients each in the ovarian, NSCLC, and cholangiocarcinoma cohorts will receive Gavo-Cel at the recommended Phase 2 dose of 1 × 108 cells/m2 after lymphedema.
Patients had to have pathologically confirmed MPM, NSCLC, severe ovarian adenocarcinoma, or cholangiocarcinoma at screening to be included in this study. Patients must also have received between 1 and 5 prior standard systemic therapies for metastatic or unresectable disease. Additional inclusion criteria included adequate organ function according to laboratory values in the clinical protocol and an ECOG performance status not greater than 1.
Gavo-cel continues to demonstrate clinical benefit in solid tumors with additional RECIST responses in ovarian cancer and mesothelioma. press release. TCR2 therapeutics. September 28, 2022. Accessed September 29, 2022. https://bit.ly/3y6jYQv