712TiP - A phase I/II multicenter, open-label, dose-escalation, safety, pharmacodynamic, and pharmacokinetic study of Q901 administered via intravenous infusion in adult patients with selected advanced solid tumors with a cohort expansion at the recommended phase II dose

Background

CDK7, part of the CAK complex regulates cell cycle progression, making it a potential therapeutic target for malignancies with aberrant cell cycle regulation. Cell cycle arrest in cancer cells affects DNA damage repair and genomic instability, potentially triggering apoptosis and anti-tumor immune response. Q901, is a potent covalent CDK7 inhibitor, with demonstrated in vivo activity against resistant models, and has potential as a treatment for various cancers where standard care has failed.

Trial design

This phase 1/2 multicenter, open-label study (NCT05394103) evaluates the safety, pharmacodynamics, and pharmacokinetics of Q901 in adult patients with solid tumors in the USA and Korea. In phase 1 dose escalation, Q901 is administered intravenously once weekly for four weeks, then once every two weeks in patients with advanced or metastatic ovarian, CRPC, HR⁺ HER2^- breast, endometrial, colorectal, small-cell lung, or pancreatic cancers. The study will establish the MTD, DLT, and RP2D of Q901 monotherapy, using a modified Toxicity Probability Interval (mTPI) design targeting a DLT rate of ∼30%. Up to 6 dose levels/50 patients will be evaluated in phase 1. Upon determining the RP2D, the study advances to phase 2. Cohort 1 will recruit HR⁺ HER2^- breast cancer patients receiving Q901 combined with fulvestrant, who have received at prior endocrine and CDK4/6 targeted treatment, along with up to two additional prior lines of systemic anticancer therapy. Cohort 2 consists of extensive-stage SCLC patients treated with Q901 monotherapy after failing first-line standard of care. Each cohort will enroll up to 20 patients to assess safety and activity in selected cancer types.

Clinical trial identification

NCT05394103.

Editorial acknowledgement

Legal entity responsible for the study

Qurient Co. Ltd.

Funding

Qurient Co. Ltd.

Disclosure

B. Choi, J. Ahn, J. Choi, K. Ahn, S. Ryu, J. Kim, D. Yu, S-J. Lee, B. Jeon, S. Proniuk, J. Kim, K. Nam: Financial Interests, Personal, Full or part-time Employment: Qurient Co. Ltd. All other authors have declared no conflicts of interest.