First-in-Human Study of IMGC936 in Participants With Advanced Solid Tumors

Inclusion Criteria:

1. Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic non-squamous NSCLC, TNBC, CRC, gastroesophageal cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is available.

   1. NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic therapy with no more than 2 chemotherapy containing lines.
   2. TNBC: Participants must have been treated with 1 to 4 prior lines of systemic therapy for metastatic disease, excluding adjuvant therapies.
   3. CRC: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
   4. Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
   5. Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy, with no more than 2 chemotherapy containing lines.
2. Either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of Cycle 1 Day 1 (C1D1).

   * Dose escalation: Participants may have non-measurable or measurable disease
   * Dose expansion: Participants must have measurable disease
3. Age ≥ 18 years old.
4. Archival formalin-fixed paraffin-embedded (FFPE) tissue must be available. Participants may undergo a fresh tumor biopsy using a low risk, medically routine procedure to obtain a specimen for testing if a tumor sample is not available.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG performance status is an inappropriate performance measurement for participant enrollment (for example, chronically non-ambulatory), then Karnofsky performance status must be ≥ 70.
6. Life expectancy ≥ 12 weeks.
7. Acceptable laboratory parameters as follows:

   * Platelet count ≥ 75 × 1000/microliter (μL) without transfusion within 28 days prior to initiation of study drug.
   * Absolute neutrophil count ≥ 1.5 × 1000/μL in the absence of any growth factor support within 21days prior to initiation of study drug.
   * Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN); for participants with hepatic metastases, ALT and AST ≤ 5 × ULN.
   * Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert's syndrome, who may enroll if the conjugated bilirubin is within normal limits.
   * Estimated glomerular filtration rate (eGFR) \>30 milliliters (mL)/ minute (min)/1.73 square meter (m\^2) or an estimated creatinine clearance of \>30 mL/min.
   * Urinalysis protein and white occult blood cells within normal limits.
   * Negative serum pregnancy test for females of childbearing potential (FOCBP).
8. FOCBP, defined as not surgically sterilized (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) and between menarche and 1-year post menopause, must have a negative serum pregnancy test performed within 72 hours prior to initiation of study drug administration. Female participants must abstain from egg donation during the study.
9. FOCBP and male participants with partners of FOCBP must agree to use highly effective methods of contraception, from the time of consent through 28 weeks after discontinuation of study drug administration. Male participants must abstain from sperm donation during the study.
10. FOCBP is not pregnant or breastfeeding, or a male participant is not expecting to father children within the projected duration of the study, starting with screening visit through 28 weeks after the last dose of study drug.

Exclusion Criteria:

1. Active central nervous system (CNS) disease within the last 6 months.
2. Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision.
3. Participants who had prior therapies within the specified times below:

   * Systemic antineoplastic therapy at least 5 half-lives or 4 weeks (whichever is shorter) prior to initiation of study drug.
   * Mediastinal or pelvic radiation therapy within 6 weeks prior to initiation of study drug administration. Palliative, limited field radiation for symptom control to soft tissues, or bone lesions within 2 weeks prior to initiation of study drug.
4. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
5. Clinically significant cardiovascular disease including but not limited to:

   * Myocardial infarction or unstable angina within 6 months prior to initiation of study drug.
   * Stroke or transient ischemic attack within 6 months prior to initiation of study drug.
   * Current clinically significant cardiac arrhythmias, for example, atrial fibrillation that are not well controlled with optimal medical intervention.
   * Current uncontrolled hypertension: systolic blood pressure \> 160 millimeters of mercury (mmHg), diastolic blood pressure \> 100 mmHg.
   * Current congestive heart failure (New York Heart Association class III-IV).
   * Current pericarditis or clinically significant pericardial effusion.
   * Current myocarditis.
   * Left ventricular ejection fraction (LVEF) of \< 50% by scan
   * QTc interval \> 480 milliseconds (msec)
6. Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a requirement for supplemental oxygen (excluding for sleep apnea) or history of ≥ Grade 3 drug-induced or radiation pneumonitis.
7. Serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   * Active hepatitis B or C infection (whether or not on active antiviral therapy).
   * Human immunodeficiency virus infection.
   * Cytomegalovirus infection.
   * Active COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards.
   * Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to initiation of study drug.
8. History of prior bone marrow, stem cell, or solid organ transplantation.
9. Second primary invasive malignancy that has not been in remission for greater than 2 years except nonmelanoma skin cancer; cervical carcinoma in situ on biopsy; or squamous intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score \< 6); or resected melanoma in situ.
10. Major trauma or major surgery within 4 weeks prior to initiation of study drug.
11. Any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the study site.
12. Known hypersensitivity to any ingredient or any excipient contained in the drug formulation
13. Vaccination with any live virus vaccine within 4 weeks prior to initiation of study drug. Inactivated annual influenza vaccination is allowed.