MC# 22-07 - A Phase I, Open-Label, Multicenter, Dose Escalation Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of IMM2902 in Patients with HER2-Expressing Advanced Solid Tumors
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Agent(s): IMM2902
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Disease Type(s): Breast, Gastric, Solid Tumor, Gastroesophageal Junction
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Phase(s): I
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Drug Classification(s): Immunotherapy, Targeted Therapy, Bispecific Antibodies
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Molecular Target(s): ERBB2 (HER2), CD47
Mechanism of Action
IMM2902 is a bispecific antibody designed to bind to and block CD47, a cell surface protein that inhibits the immune response, and also bind to ERBB2, a protein found on the cell surface of certain tumors.
Purpose
In this study, the sponsor and investigators want to learn:
- How much of IMM2902 can be given with an acceptable level of side effects
- The effects of IMM2902 (good and bad)
- How much of IMM2902 is absorbed into the blood and how fast it is removed
- If research tests can be used in the future to predict who will benefit from IMM2902
Inclusion Criteria
- Part 1: Histologically or cytologically confirmed HER2-expressing (HER2 IHC 3+, 2+ or 1+) advanced solid malignancy, including but not limited to breast, gastric/GEJ, ovarian, colorectal, and non-small cell lung, who have been treated with at least one regimen of prior systemic therapy, or who refuse systemic therapy, and for which there is no curative therapy available
- Cohort 1: histologically confirmed HER2-positive (HER2 IHC 3+ or HER2 IHC 2+/ISH-positive) locally advanced (unresectable) and/or metastatic breast cancer who have progression on or after at least 2 prior lines of anti-HER2 directed therapy with mandatory trastuzumab, petuzumab and T-DM1 or other anti-HER2 therapy
- Cohort 2: Histologically confirmed HER2-low (HER2 IHC 1+ or HER2 IHC 2+/ISH-negative) locally advanced (unresectable) and/or metastatic breast cancer who have progression after 2 or more lines of systemic therapy
- Cohort 3: Histologically confirmed HER2-positive (HER2 IHC 3+ or HER2 IHC 2+/ISH-positive) locally advanced (unresectable) and/or metastatic gastric/GEJ cancer who have progression on or after at least one prior first-line therapy, including prior fluoropyrimidine + platinum and mandatory prior trastuzumab or other prior anti- HER2 (including investigational) therapy. Patients did not receive ≥2 prior regimens; these patients will be eligible for second-line anti-HER2 therapy.
- Cohort 4: Histologically confirmed HER2-low (HER2 IHC 1+ or HER2 IHC 2+/ISH-negative) locally advanced (unresectable) and/or metastatic gastric/GEJ cancer who have progression after 2 or more lines of systemic therapy
- Cohort 5: Histologically confirmed HER2-positive (HER2 IHC 3+ or HER2 IHC 2+/ISH-positive) any other solid tumor types, including but not limited colorectal cancer, non-small cell lung (NSCLC), ovarian cancers, that are not breast or gastric/GEJ cancers who have documented progression after standard therapy
- HER2-expressing testing is defined as follows:
- Part 1: HER2-expressing is defined as HER2 3+, 2+ or +1 expression by IHC with or without gene amplification by ISH performed upon the primary tumor or metastatic lesion based upon the assessment by a qualified local or central pathology laboratory. Documentation of HER2 status should be available at registration.
- Part 2: HER2-positive is defined as HER2 3+ expression by IHC or HER2 IHC2+/ISH-positive (required for Part 2: Cohorts 1, 3 and 5). HER2-low is defined as HER2 1+ expression by IHC or HER2 IHC2+/ISH-negative (required for Part 2: Cohorts 2 and 4). (Appendix 4 and Appendix 5). HER2 testing is performed upon the primary tumor or metastatic lesion based upon the assessment and confirmation by a central pathology laboratory. FDA approved tests will be used to determine HER2 tumor expression for all patients enrolling in this study (Appendix 6).
- Phase 1b only: Willing to consent to 1 mandatory pre-treatment tumor biopsy for HER2 expression assessment, unless determined to not be feasible by the Investigator (reasons include, but are not limited to, lack of accessible tumor tissue to biopsy and patient safety issues). Part 2 Cohort 1, Cohort 3 and Cohort 5 patients must undergo new biopsy to confirm HER2- positive tumor status for eligibility.
- Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: Part 1: Has at least non-irradiated evaluable disease (target or non-target lesions) per RECIST version 1.1. Part 2: Has at least non-irradiated measurable disease (target lesions) per RECIST version 1.1.
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
Exclusion Criteria
- Prior treatment with CD47 or SIRPα-targeting agents
- Anthracyclines within 3 months before first IMM2902 dosing or lifetime load exceeding 300mg/m² adriamycin or equivalent
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
