A Phase 1 Study of IM-1617 in Participants With Advanced Cancer

This is a Phase 1 open-label, multicenter, dose escalation and expansion study designed to determine the safety, tolerability, PK, and preliminary antitumor activity of IM-1617 administered to participants with unresectable locally advanced or metastatic solid tumors. The study consists of 2 parts:

Part A: A dose-escalation phase to evaluate the safety and tolerability of IM-1617 to determine the recommended dose for expansion (RDE), evaluate maximum tolerated dose, and maximum achievable dose of IM-1617 in up to approximately 75 participants.

Part B: An expansion phase to further evaluate the safety and preliminary antitumor activity of IM-1617 monotherapy at the RDE and one or more other dose regimens in up to 4 indication-specific cohorts. Up to approximately 100 participants will be enrolled in Part B.

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Part A: Histological diagnosis of one of the following unresectable locally advanced or metastatic solid tumors:

• CRC, all subtypes
• NSCLC:

• Non-squamous cell carcinoma subtypes, such as adenocarcinoma
• Squamous cell carcinoma subtype
• Breast cancer (subtypes based on estrogen/progesterone receptor and HER2 testing according to American Society of Clinical Oncology - College of American Pathologists guidelines):

• Triple-negative breast cancer
• HR+, HER2- subtype
• Esophageal, esophagogastric junction, and gastric cancer:

• Adenocarcinoma subtype
• Other histologies, if approved by the Medical Monitor, which may include: head and neck squamous cell carcinoma; cervical cancer; bladder cancer; squamous cell carcinoma subtype of esophageal, esophagogastric junction, and gastric cancer; HER2+ breast cancer
• Part B Cohorts - Histological diagnosis of one of the following unresectable locally advanced or metastatic solid tumors:

• Cohort B1: CRC, all subtypes
• Cohort B2: NSCLC

• Non-squamous cell carcinoma subtypes, such as adenocarcinoma
• Squamous cell carcinoma subtype
• Cohorts B3 and B4: Cohort-specific disease indications may include those listed for Part A
• Participants must have disease that is considered to be noncurative and meet the appropriate criteria below:

• Part A only: Participants have progressed on, were intolerant to, or have a contraindication to prior SOC treatments, with no satisfactory SOC treatment options available.
• Part B only:

• Cohort B1 (CRC):

• Participants must have previously progressed on, were intolerant to, or have a contraindication to fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, bevacizumab, and for those with RAS wild-type tumors, an anti-epidermal growth factor receptor (EGFR)-directed monoclonal antibody in advanced disease setting.
• Participants with actionable biomarkers must have been treated with at least one prior appropriate biomarker-directed therapy.
• If any of these therapies was given in the adjuvant setting, disease must have progressed within 6 months after completing therapy.
• Cohort B2 (NSCLC):

• Participants must have previously progressed on, were intolerant to, or have a contraindication to platinum-based chemotherapy and a programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibody (given concurrently or sequentially with chemotherapy) in advanced disease setting.
• Participants with actionable biomarkers must have been treated with at least one prior appropriate targeted therapy.
• If any of these therapies was given in the adjuvant setting, disease must have progressed within 6 months after completing therapy.
• Cohorts B3 and B4: Criteria will be specified based on the disease indications selected.
• Participants must have measurable disease as defined per RECIST v1.1

Exclusion criteria

• Previously treated with an antibody-drug conjugate (ADC) with a topoisomerase-1 (TOP1) inhibitor payload. Exception: Participants with NSCLC or breast cancer may have received up to one prior ADC with a TOP1 inhibitor payload
• History of anaphylactic reaction to TOP1 inhibitors (e.g., irinotecan) or TOP1 inhibiting ADCs
• Life expectancy < 12 weeks
• Prior solid organ transplant
• Symptomatic ascites or pleural effusion
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Known history of another primary solid or hematologic malignancy (other than that under study), unless the participant has undergone potentially curative therapy with no evidence of recurrence for at least 2 years and approved by the Medical Monitor