IMM2902, a HER2/SIRPα Bispecific MAb-Trap Antibody-receptor Fusion Protein, in Patients with HER2-expressing Advanced Solid Tumors

Inclusion Criteria:

• Age ≥ 18 years

• Weigh greater than 30 kg

• life expectancy of at least 3 months

• Phase 1a Histologically or cytologically confirmed HER2-expressing advanced solidmalignancy, who have been treated with at least one regimen of prior systemictherapy, or who refuse systemic therapy, and for which there is no curative therapyavailable.

• Phase 1b Histological Diagnsis There will be 5 cohorts:

Cohort 1: Histologically confirmed HER2 overexpression (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 trastuzumab, pertuzumab, tucatinib, Fam-trastuzumab deruxtecan-nxki and T-DM1 or other anti-HER2 therapy.

Cohort 2: Histologically confirmed HER2-low (HER2 IHC 1+ or HER2 IHC 2+/ISH-negative and/or HER2 gene amplification in tumor specimen or in circulating tumor cells by ISH, NGS, or ctDNA-NGS) locally advanced (unresectable) and/or metastatic breast cancer who have progression after 2 or more lines of systemic therapy.

Cohort 3: Histologically confirmed HER2 overexpression (HER2 IHC 3+ or HER2 IHC 2+/ISH-positive) locally advanced (unresectable) and/or metastatic gastric/esophageal/gastroesophageal junction (GEJ) cancer who have progression on or after at least one prior therapy, including prior fluoropyrimidine + platinum and prior trastuzumab, and/or fam-trastuzumab deruxtecan-nxki or other prior anti-HER2 (including investigational) therapy.

Cohort 4: Histologically confirmed HER2-low (HER2 IHC 1+ or HER2 IHC 2+/ISH-negative and/or HER2 gene amplification in tumor specimen or in circulating tumor cells by ISH, NGS, or ctDNA-NGS) locally advanced (unresectable) and/or metastatic gastric/esophageal/gastroesophageal junction (GEJ) cancer who have progression after 2 or more lines of systemic therapy.

Cohort 5: Histologically confirmed HER2 overexpression (HER2 IHC 3+ or HER2 IHC 2+/ISH-positive) any other solid tumor types, including but not limited to colorectal cancer, non-small cell lung (NSCLC), ovarian cancers, that are not breast

• Has at least non-irradiated evaluable disease (target or non-target lesions) perRECIST version 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

• Completion of prior chemotherapy systemic anticancer therapy at least 2 weeks priorto study entry.

• Radiation therapy must be completed at least 2 weeks prior to study entry. Radiatedlesions may not serve as measurable disease unless they have been radiated ≥12months prior to enrollment.

• Patients may have parenchymal brain metastases if stable (no evidence ofprogression) for at least 1 month after local therapy (radiation or surgery).Leptomeningeal disease is excluded.

• Patients must have adequate organ and bone marrow function within 14 days of firstdose of study drug administration

• Female subject must either be of non-reproductive potential or must have a negativeurine or serum prenancy test within 7 days prior to the first dose of IMM2902.

Exclusion Criteria:

• Prior anti-cancer therapy including chemotherapy, hormonal therapy, orinvestigational agents within 2 weeks or within at least 4 half-lives prior toIMM2902 dosing (up to a maximum of 4 weeks).

• Prior treatment with neoadjuvant or adjuvant anthracyclines within cumulative doseof doxorubicin of >400 mg/m2 or epirubicin of >800 mg/m².

• Prior treatment with CD47 or SIRPα-targeting agents.

• Trastuzumab, pertuzumab, lapatinib, tucatinib, fam-trastuzumab deruxtecan-nxki orT-DM1 within 3 weeks before first IMM2902 dosing.

• Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapywith the exception of alopecia, vitiligo, and the laboratory values defined in theinclusion criteria.

• Mean QT interval corrected for heart rate (QTc) ≥ 450 ms for males or QTc ≥ 470 msfor females calculated from 2 electrocardiograms (ECGs) using Fridericia's formula.Two EKGs 5 minutes (+/-2 min) apart are mandatory.

• Active or prior documented autoimmune or inflammatory disorders (includinginflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [withthe exception of diverticulosis], systemic lupus erythematosus, Sarcoidosissyndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,rheumatoid arthritis, hypophysitis, uveitis, etc]).

• Symptomatic congestive heart failure New York Heart Association (NYHA) FunctionClassification II-IV, uncontrolled hypertension, acute myocardial infarction withinthe last 6 months, unstable angina pectoris, cardiac arrhythmia.

• Uncontrolled diabetes mellitus, Interstitial lung disease, serious gastrointestinalconditions associated with diarrhea.

• Pulmonary embolism or deep vein thrombosis within 3 months prior to the first doseof study drug.

• Uncontrolled pulmonary, renal, or hepatic dysfunction.

• Ongoing or active infection requiring systemic treatment.

• Psychiatric illness/social situations that would limit compliance with studyrequirements, substantially increase risk of incurring AEs or compromise the abilityof the patient to give written informed consent.

• Any other illness or condition that the treating investigator feels would interferewith study compliance or would compromise the patient's safety or study endpoints.

• Second malignancy, except treated basal cell or localized squamous skin carcinomas,localized prostate cancer, or other malignancy for which treatment was completed atleast 3 years ago and for which there is no evidence of recurrence.

• Known allergic reactions to any component or excipient of IMM2902 or known allergicreactions to trastuzumab or other prior anti-HER2 (including investigational) orother monoclonal antibody ≥ Grade 3.

• Patients requiring concomitant therapeutic anticoagulation, excluding those takinglow dose of anticoagulation agents for diseases such as pulmonary embolism, deepvenous thrombosis.

• Known active infection including tuberculosis, hepatitis B, hepatitis C, or humanimmunodeficiency virus.

• Known inherited or acquired bleeding disorders.

• History of hemolytic anemia or Evans syndrome, sickle cell disease, thalassemia,G6PD deficiency, hereditary spherocytosis, or hypersplenism in the last 3 months.

• Current or prior use of immunosuppressive therapy within 14 days before the firstdose of IMM2902.

• Receipt of live attenuated vaccination within 30 days prior to registration.