Dose-Limiting Toxicities: Theseus Pharma Terminates THE-630 Study For Gastrointestinal Cancer

Theseus Pharmaceuticals Inc THRX will discontinue enrollment in the ongoing phase 1/2 study and terminate the development of THE-630 in patients with gastrointestinal stromal tumors (GIST).

Two patients in Cohort 7 had cleared the dose-limiting toxicity (DLT) observation period without experiencing a DLT.

Following the data release on May 25, the third patient enrolled in Cohort 7 experienced grade 3 hand-foot skin reaction (HFSR), which required an expansion of the cohort to 6 patients. 

Subsequently, one patient in the Cohort 7 expansion group experienced grade 2 HFSR, which required a dose interruption of ≥7 days. 

The company does not believe that THE-630 has a differentiated profile at doses below 27 mg, which would provide exposure well below the target level of 100 nanomolar average concentration. 

As a result, the company has decided to terminate the development of THE-630 in GIST.

As of July 10, 32 patients were treated with THE-630 across 7 doses (3 mg to 27 mg). Six patients developed grade 1 to 3 HFSR (3 patients in the 27 mg cohort, two in the 18 mg cohort, and one initially in the 9 mg cohort after intra-patient dose escalation to 18 mg). 

Grade 3 HFSR was only observed in a patient who started treatment at 27 mg. HFSR was not observed at doses of 12 mg or lower. 

No significant skin toxicity was observed in preclinical toxicology studies. 

The company is analyzing data to inform the feasibility of developing low-dose THE-630 for KIT-associated mast cell-driven inflammatory indications.

Theseus is prioritizing THE-349 for EGFR mutant non-small cell lung cancer; IND is on track for submission in Q4 2023.

The company also announced a new program targeting KIT for patients with early-line GIST; development candidate nomination is expected in H1 2024.

Development candidate nomination from the BCR-ABL program is also expected in H1 2024.

$234 million in cash, cash equivalents, and marketable securities as of June 30, 2023, is expected to provide a cash runway into 2026.

Price Action: THRX shares are down 65.50% at $3.28 during the premarket session on the last check Friday.