A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- vobramitamab duocarmazine
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Sponsor
- MacroGenics
- Enrollment
- 143
- Locations
- 21
- Primary Endpoint
- Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03
- Status
- Terminated
- Last Updated
- 9 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
- •Eastern Cooperative Oncology Group performance status of ≤2
- •Life expectancy ≥ 12 weeks for dose escalation phase and ≥ 24 weeks for cohort expansion phase
- •Measurable disease. Prostate cancer patients with bone only disease are eligible.
- •Acceptable laboratory parameters and adequate organ reserve.
- •Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical benefit is available.
- •Module A Cohort Expansion:
- •mCRPC that has progressed with one prior line of chemotherapy for metastatic disease and no more than two prior lines of anti-hormonal therapy.
- •NSCLC: metastatic disease after standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than 2 prior lines of chemotherapy.
- •TNBC: Locally advance or metastatic disease that has progressed following at least one systemic therapy.
Exclusion Criteria
- •Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on MRI, CT or PET within 6 months, or history of leptomeningeal disease or cord compression at the time of enrollment.
- •Prior treatment with B7-H3 targeted agents for cancer.
- •Treatment with systemic cancer therapy, biologic agents, or anti-hormonal therapy (mCRPC) within 4 weeks, prior small molecule targeted or kinase inhibitors within 14 days or 5 half-lives, prior radioligand within 6 months
- •Clinically significant cardiovascular disease.
- •Clinically significant pulmonary compromise or requirement for supplemental oxygen.
- •History of clinically-significant cardiovascular disease, including but not limited to pericarditis or pericardial effusion.
- •Active viral (including confirmed or presumed COVID-19), bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration.
- •Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
- •Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- •Major trauma or major surgery within 4 weeks of first study drug administration.
Arms & Interventions
Cohort 1
0.5 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Cohort 2
1.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Cohort 3
2.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Cohort 4
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Cohort 5
4.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
mCRPC expansion
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
NSCLC expansion
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
TNBC expansion
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Melanoma expansion
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
SCCHN expansion
3.0 mg/kg IV every 3 weeks
Intervention: vobramitamab duocarmazine
Outcomes
Primary Outcomes
Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03
Time Frame: Throughout the study up to 24 months
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
Number of Participants With Dose Limiting Toxicities (DLT)
Time Frame: up to 42 days from first dose
Number of participants with severe side effects from study treatment during the DLT evaluation period (6 weels)
Secondary Outcomes
- Best Overall Response (BOR) of Vobramitamab Duocarmazine(Throughout the study for up to 24 months)
- Objective Response Rate (ORR) of Vobramitamab Duocarmazine(Efficacy evaluations every 9 weeks throughout the study for up to 24 months)
- Progression Free Survival (PFS) of Vobramitamab Duocarmazine(Every 9 weeks for up to 24 months)
- Median Duration of Response (DoR) of Vobramitamab Duocarmazine(Throughout the study for up to 48 months)
- Median Overall Survival (OS) of Vobramitamab Duocarmazine(Every 9 weeks for up to 24 months)
- PSA Response Rate(Every 3 weeks up to 24 months)
- Best PSA Response(Every 3 weeks up to 24 months)
- Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC)(At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).)
- Mean AUC of Duocarmycin(At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).)
- Mean Maximum Concentration Vobramitamab Duocarmazine ADC(At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.)
- Mean Maximum Concentration Duocarmycin(At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.)
- Mean Trough Concentration of Vobramitamab Duocarmazine ADC(At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).)
- Mean Trough Concentration of Duocarmycin(At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).)
- Number of Participants Who Develop MGC018 Anti-drug Antibodies(Every 3 weeks through end of treatment, up to 24 months)