A Phase 1, Open-Label, Multicenter, Dose Escalation Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of IMM2902 in Patients with HER2-Expressing Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- IMM2902
- Conditions
- Advanced Solid Tumor
- Sponsor
- ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
- Enrollment
- 135
- Locations
- 3
- Primary Endpoint
- Dose-Limiting Toxicity (DLT)
- Status
- Suspended
- Last Updated
- last year
Overview
Brief Summary
This trial is a first-in-human, open label, multi-center, dose escalation phase 1a study followed by a disease-specific dose expansion phase 1b study to evaluate the safety, efficacy, and pharmacokinetics (PK) of IMM2902, a HER2/SIRPα bispecific mAb-Trap antibody-receptor fusion protein, in patients with HER2-expressing advanced solid tumor.
Investigators
Eligibility Criteria
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 solid malignancy, 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.
- •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
Exclusion Criteria
- •Prior anti-cancer therapy including chemotherapy, hormonal therapy, or investigational agents within 2 weeks or within at least 4 half-lives prior to IMM2902 dosing (up to a maximum of 4 weeks).
- •Prior treatment with neoadjuvant or adjuvant anthracyclines within cumulative dose of 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 or T-DM1 within 3 weeks before first IMM2902 dosing.
- •Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- •Mean QT interval corrected for heart rate (QTc) ≥ 450 ms for males or QTc ≥ 470 ms for 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 (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]).
- •Symptomatic congestive heart failure New York Heart Association (NYHA) Function Classification II-IV, uncontrolled hypertension, acute myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia.
- •Uncontrolled diabetes mellitus, Interstitial lung disease, serious gastrointestinal conditions associated with diarrhea.
- •Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
Arms & Interventions
IMM2902
IMM2902 Phase 1a Dose escalation: 0.03, 0.1, 0.25, 0.5, 1.0, 1.5, and 2.0 mg/kg through intravenous administration weekly up to 48 weeks. Phase 1b Dose expansion: A disease-specific dose expansion study in patients with locally advanced (unresectable) and/or metastatic breast with HER2-overexpression (Cohort 1) or HER2-low (Cohort 2), gastric/esophageal/gastroesophageal junction (GEJ) cancer with HER2-overexpression (Cohort 3) or HER2-low (Cohort 4) and other solid tumors with HER2-overexpression (Cohort 5) is aimed at further defining safety and characterizing efficacy. Dose expansion is through intravenous administration weekly up to 48 weeks.
Intervention: IMM2902
Outcomes
Primary Outcomes
Dose-Limiting Toxicity (DLT)
Time Frame: 48 Weeks
All toxicities will be graded according to the NCI CTCAE Version 5.0, which provides additional guidance for AEs not specifically mentioned in CTCAE. A DLTs is defined as any Grade 3 or greater AE that is assessed as related to study treatment that occurs during the 4-week DLTs observation period.
maximum tolerated dose (MTD) of IMM2902
Time Frame: 48 Weeks
Toxicity will be evaluated according to the NCI CTCAE Version 5.0.
dose for expansion (RDE) of IMM2902
Time Frame: 48 Weeks
Toxicity will be evaluated according to the NCI CTCAE Version 5.0.
Number of patients with Adverse Events（AEs）
Time Frame: 48 Weeks
Graded according to the NCI CTCAE V5.0