A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M17D1 in Subjects With HER2-Expressing or HER2-Mutant Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- BL-M17D1
- Conditions
- Not specified
- Sponsor
- SystImmune Inc.
- Enrollment
- 120
- Locations
- 9
- Primary Endpoint
- Participants with Dose-limiting toxicities
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The objective of this study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BL-M17D1 in patients with HER2-Expressing or HER2-Mutant Advanced or Metastatic Solid Tumors.
Detailed Description
BL-M17D1-ST-101 is a multicenter, Phase 1 study evaluating the safety, tolerability, pharmacokinetic profile, and initial efficacy of BL-M17D1 in subjects with unresectable locally advanced or metastatic HER2-expressing or HER2-mutant solid tumors. This study will be conducted in three parts (dose escalation, dose finding and dose expansion). BL-M17D1 will be administered on Day 1 and Day 8 of a continuous 21-day treatment cycle.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed the informed consent form
- •Age ≥18 years.
- •Weighs more than 40 kg. For doses \<0.3 mg/kg, subject must weigh ≥70 kg.
- •Has a life expectancy of ≥3 months.
- •Has documented locally advanced or metastatic HER2-positive solid tumor(s) (IHC 1+ to 3+ or in situ hybridization \[ISH\] positive) or HER2-mutant tumor specimen not amenable to curative surgery or radiation and has received at least 1 line of standard therapy in the advanced/metastatic setting, or for which no standard treatment is available, including:
- •Cohort 1: HER2-positive breast cancer (BC);
- •Cohort 2: HER2-positive gastric/gastroesophageal junction cancer (GC/GEJ);
- •Cohort 3: HER2-positive or HER2-mutant non-small cell lung cancer (NSCLC);
- •Cohort 4: HER2-positive endometrial cancer (EC);
- •Cohort 5: HER2-positive ovarian cancer (OC), including fallopian tube cancer and primary peritoneal cancer;
Exclusion Criteria
- •Subjects who meet any of the following criteria will not be eligible for participation in this study:
- •Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration.
- •Concomitant use of strong inhibitors and inducers of any CYP3A4 enzyme or P-gp transporter system within 2 weeks or 5 half-lives (whichever is longer) prior to the first administration and throughout all parts of the study.
- •History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure at any time, or history of myocardial infarction or unstable angina pectoris within 6 months before enrollment.
- •Prolonged QT interval (QTcF \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block, or a history of additional risk factors for torsades de pointes (TdP; eg, heart failure as defined in Exclusion Criterion 3, chronic or recurrent hypokalemia that requires medical intervention, congenital long QT syndrome, family history of long QT syndrome) or any current concomitant medication known to prolong the QT/QTc interval or cause TdP.
- •Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type 1 diabetes, hypothyroidism that can be controlled by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
- •Other prior malignancies except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years prior to screening.
- •Poorly controlled hypertension by two types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg).
- •Advanced or clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease and asthma, restrictive lung disease, pulmonary hypertension etc.
- •Have a history of noninfectious interstitial lung disease (ILD)/pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Arms & Interventions
Dose Escalation
Beginning with Cycle 1, BL-M17D1 will be administered on Day 1 and Day 8 by (IV) infusion every 3 weeks (D1,D8 Q3W)
Intervention: BL-M17D1
Dose Finding
Beginning with Cycle 1, BL-M17D1 will be administered on Day 1 and Day 8 by (IV) infusion every 3 weeks (D1,D8 Q3W)
Intervention: BL-M17D1
Dose Expansion
Beginning with Cycle 1, BL-M17D1 will be administered on Day 1 and Day 8 by (IV) infusion every 3 weeks (D1,D8 Q3W)
Intervention: BL-M17D1
Outcomes
Primary Outcomes
Participants with Dose-limiting toxicities
Time Frame: 1 Year
Measuring the number of patients Dose-limiting toxicities (DLTs). A DLT is defined as any of the following events that are not clearly due to the underlying disease or extraneous causes: Hematologic toxicities * Grade 4 neutrophil count decreased lasting \>7 days * Grade ≥3 febrile neutropenia of any duration * Grade ≥3 platelet count decreased with clinically significant hemorrhage * Grade 4 thrombocytopenia lasting \>7 days Nonhematologic toxicities * Death not clearly related to disease progression or extraneous cause * Hy's law cases * Grade ≥3 nonhematologic toxicities
Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs)
Time Frame: 1 Year
Measuring the number of patients with serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
To determine the MTD if reached or MAD and two or more RDEs of BL-M17D1
Time Frame: 1 Year
MTD, MAD, and RDE