Injection of IP-001 Into Thermally Ablated Hepatic Tumors in Patients With Colorectal Liver Metastases

This is a Phase 2/3, three-arm, dose finding, randomized, controlled, patient-blinded, international, adaptive design study in patients with liver-only metastatic colorectal cancer. The purpose is to investigate the efficacy and safety of the two different dose concentrations of IP-001 for Injection administered intratumorally following standard of care (SOC) complete thermal ablation of liver tumors with microwave ablation (MWA) compared SOC MWA alone. MWA alone is selected as the control because, in patients with liver-only metastatic colorectal cancer treated with curative intent, MWA is an accepted SOC therapeutic strategy and routine continuation of systemic therapy in this context is not mandated by guidelines and remains heterogeneous across institutions.

The study is designed with a seamless transition from Phase 2 to the Phase 3 based on prespecified dose selection and interim efficacy and safety criteria. Phase 2 will include three-arms: MWA alone, MWA plus 10 mg/ml IP-001, or MWA plus 1 mg/ml IP-001. Crossover from the Control Arm to an Experimental Arm is not allowed. Phase 3 will continue to be randomized between the MWA alone (control) and the MWA plus IP-001 dose selected based on the Phase 2 interim (futility) analysis.

The trial will consist of the following three periods described below.

1. Screening Period: Up to 28 days for screening assessments to determine study eligibility. 2. Treatment and Follow-up Period: On Treatment Day 1, in a single session, all patients will undergo SOC hepatic tumor MWA with predetermined margins. Immediately following ablation, patients in the Experimental Arms will receive the appropriate dose of IP-001 intratumorally into all ablated tumor(s). Blood samples will be taken before treatment starts, and then again on various days after treatment to help check for important blood markers in and how the drug works in the body. In addition, patients will undergo post-treatment efficacy and safety and tolerability efficacy assessments for 12 weeks before patients move on to standard surveillance monitoring. 3. Surveillance Period: Patients will be followed for efficacy, concomitant medication and procedures, and survival, every 3 months for the first year, and then every 6 months thereafter for 5 years after the initial treatment.

Patients who develop a new or recurrent tumor(s) may be eligible receive additional treatment, as appropriate, including study retreatment, other standard liver treatments, or systemic anti-cancer therapy. Patients will be followed for subsequent anticancer therapies/procedures, progression, and survival status, as indicated, for 5 years after the original treatment day to help researchers determine if IP-001 will improve a patient's response to other cancer therapies.