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

Prior treatment

• 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
• Prior solid organ transplant

Other illness

• History of anaphylactic reaction to TOP1 inhibitors (e.g., irinotecan) or TOP1 inhibiting ADCs
• Known history of another primary solid or hematologic malignancy (other than that under study), unless the participant has undergone definitive/curative therapy, has had no evidence of recurrence and has negligible risk of metastatic disease of death, with approval by the Medical Monitor

Other

• Life expectancy \< 12 weeks
• Symptomatic ascites or pleural effusion
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

• 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 were given in the adjuvant setting, disease must have progressed within 6 months after completing therapy.
  • Participants must not have received more than 3 prior lines of systemic therapy (excluding targeted therapies for actionable biomarkers).
  • 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 were given in the adjuvant setting, disease must have progressed within 6 months after completing therapy.
  • Participants must not have received more than 2 prior lines of systemic therapy (excluding targeted therapies for actionable biomarkers).
  • 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