Summary

This study is a Phase 1/2, first-in-human, open-label, dose-escalation, and expansion
study designed to characterize the safety, tolerability, pharmacokinetics,
immunogenicity, and preliminary antitumor activity of IMGC936 administered by intravenous
(IV) infusion.

Objectives

This is an open-label, dose-escalation, and expansion study to determine the Maximum
Tolerated Dose (MTD) and select the recommended phase 2 dose. Dose escalation follows a
conventional 3+3 design; successive cohorts of 3 to 6 participants each will be evaluated
in sequential escalating doses of single-agent IMGC936. Upon completion of the
dose-escalation phase of the study, following determination of the recommended Phase 2
dose (RP2D), up to 5 expansion cohorts may be opened in tumor types selected from those
enrolled in dose escalation.

Participants with relapsed or refractory, unresectable locally advanced or metastatic
solid tumors including non-squamous non-small cell lung cancer (NSCLC), triple-negative
breast cancer (TNBC), colorectal cancer (CRC), gastroesophageal cancer, or pancreatic
cancer will be enrolled.

IMGC936 is administered via intravenous (IV) infusion on Day 1 of Cycle 1 and every
subsequent 21-day cycle thereafter, at the assigned dose for each cohort during dose
escalation, and at the RP2D for expansion. Infusion duration will vary depending on dose
and participant tolerability.

Sentinel dosing will be used for the first 2 dose levels of dose escalation. The first
administration of IMGC936 in participants at the first 2 dose levels of dose escalation
will be staggered by at least 48 hours. The dose-limiting toxicity (DLT) evaluation
period is 21 days. Participants may continue on study drug until disease progression,
adverse event (AE) requiring discontinuation, DLT during evaluation window, pregnancy,
death, investigator decision, lost to follow up (LTFU), major protocol deviation
requiring discontinuation, withdrawal of consent, or sponsor, investigator or regulatory
agency terminates the study.

Tumor assessments are performed every 6 weeks (Q6W) while on study drug then every 12
weeks (Q12W). Tumor assessments continue until discontinuation criteria are met. If
feasible, participants who discontinue study drug for reasons other than progressive
disease (PD) (e.g., toxicity) should continue to undergo tumor assessments Q12W as
post-treatment follow up until evidence of PD, initiation of another anticancer therapy,
withdrawal of consent, LTFU, death, or end of study. Post-treatment follow up also
includes following ongoing treatment emergent adverse events (TEAEs) until the event has
resolved to baseline grade, the event is assessed by the investigator as stable,
initiations of another anticancer therapy, withdrawal of consent, LTFU, death, or it has
been determined that study drug or participation is not the cause of the AE.

Eligibility

1. Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer (CRC), gastroesophageal cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is available.
2. NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic therapy with no more than 2 chemotherapy containing lines.
3. TNBC: Participants must have been treated with 1 to 4 prior lines of systemic therapy for metastatic disease, excluding adjuvant therapies.
4. CRC: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
5. Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
6. Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy, with no more than 2 chemotherapy containing lines.
7. Either measurable or non-measurable disease per RECIST 1.1 and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of C1D1.
8. Dose escalation: Participants may have non-measurable or measurable disease
9. Dose expansion: Participants must have measurable disease
10. Age = 18 years old.
11. 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.
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG performance status is an inappropriate performance measurement for participant enrollment (eg, chronically non-ambulatory), then Karnofsky performance status must be = 70.
13. Life expectancy = 12 weeks.
14. Acceptable laboratory parameters as follows:
15. Platelet count = 75 × 1000/µL without transfusion within 28 days prior to initiation of study drug.
16. Absolute neutrophil count = 1.5 × 1000/µL in the absence of any growth factor support within 21days prior to initiation of study drug.
17. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 3.0 × upper limit of normal (ULN); for participants with hepatic metastases, ALT and AST = 5 × ULN.
18. Total bilirubin = 1.5 × ULN, except participants with Gilbert's syndrome, who may enroll if the conjugated bilirubin is within normal limits.
19. Estimated glomerular filtration rate (eGFR) >30mL/min/1.73m2 or an estimated creatinine clearance of >30 mL/min.
20. Urinalysis protein and white occult blood cells within normal limits.
21. Negative serum pregnancy test for females of childbearing potential (FOCBP).
22. 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.
23. 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.
24. 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.

Treatment Sites in Georgia