A Phase 1/2 Study to Investigate CRB-701 in Solid Tumors

This is a three-part open-label, Phase 1/2 clinical trial designed to evaluate the safety, PK, and efficacy of CRB-701 in participants with advanced solid tumors expressing nectin-4.

Part A will include solid tumor types known to express nectin-4. Dose escalation will be guided by the Bayesian optimal interval (BOIN) design to determine the Maximum Tolerated Dose (MTD) of CRB-701. Four (4) dose groups are pre-determined. Dose escalation/de-escalation decisions are made based on the occurrence of DLT.

Part B will evaluate two dose levels of CRB-701 alone and in combination with anti-PD-1 by using a time-to-event Bayesian optimal Phase 2 study design to optimize the dose of CRB-701 in one or more separate cohorts of participants with nectin-4-positive tumors.

During Part C, the recommended dose level of CRB-701 for further exploration defined in Part B will explore CRB-701 alone or combined with anti-PD-1 in up to seven separate cohorts of participants with advanced tumors known to express Nectin-4.

Inclusion criteria

• Confirmed diagnosis of select advanced or metastatic nectin-4 expressing solid tumors that have progressed having exhausted all appropriate lines of therapy or have no other standard therapy with proven clinical benefit. In Part C, HNSCC participants may enroll as first-line therapy.

Exclusion criteria

• Active of uncontrolled CNS metastases
• History of solid tumors other than the diseases under study
• History of and/or current cardiovascular events or conditions in the previous 6 months
• Pre-existing >/= Grade 2 neuropathy
• Hemoglobin A1C (HbA1C) >/= 8%, uncontrolled diabetes mellitus or know diabetic neuropathy
• Active ocular disease at baseline
• Chronic severe liver disease or live cirrhosis
• Interstitial lung disease or pneumonitis within 6 months on initiating treatment on study
• Other significant cormorbidities.