Clinical trial NCT02689284: Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
Official title: A Phase 1b/2, Open Label, Dose Escalation Study of Margetuximab in Combination With Pembrolizumab in Patients With Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Stomach Cancer
Esophageal Cancer
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-02-23
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This main purpose of this clinical study is to learn about the safety and activity of margetuximab and pembrolizumab combination treatment in patients with HER2+ gastric and gastroesophageal junction cancer.

Detailed description: Detailed Description: Both margetuximab and pembrolizumab are monoclonal antibodies used in combination to treat HER2+ gastric and gastroesophageal junction cancer. This study has two parts: Dose Escalation and Dose Expansion. The Dose Escalation phase of the study will evaluate safety of escalating doses of the combination treatment. The Dose Expansion phase will evaluate safety and activity of the combination in patients with gastric or gastroesophageal cancer once the final dose and schedule are defined. In addition, a cohort of patients with HER2+ 3+ gastric cancer patients will be enrolled in the Dose Expansion Phase.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent.
2. Age ≥ 18 years old (or minimum age based upon local regulations)
3. Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric cancer. Gastric Cancer Expansion Phase will include only gastric cancer patients with 3+ HER2 positivity.
4. HER2+ as 3+ (as defined in AJCC staging manual 8th edition) by IHC or in-situ hybridation (ISH) amplified.
5. Have received prior treatment with trastuzumab.
6. Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
7. Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Life expectancy ≥ 12 weeks.
10. Measurable disease as per RECIST 1.1 criteria.

Exclusion Criteria:

1. Patients with symptomatic central nervous system (CNS) metastases.
2. Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
3. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
4. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
5. Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
6. Treatment with corticosteroids (≥10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
7. History of clinically-significant cardiovascular disease.
8. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
9. History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
10. Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
11. Evidence of active viral, bacterial, or systemic fungal infection.

Primary outcomes:
measure: Number of Patients With Dose Limiting Toxicities
timeFrame: 21 days
measure: Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).
timeFrame: up to 24 months
measure: Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment
timeFrame: 12 months
measure: Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria
timeFrame: 12 Months
measure: Duration of Response
timeFrame: up to 24 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 24 Months
measure: Progression Free Survival (PFS)
timeFrame: 24 Months
measure: Change From Baseline in Pharmacodynamic Markers in Whole Blood
timeFrame: from first dose to the end of treatment, average about 12 months
measure: Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment
timeFrame: from first dose to the end of treatment, average 12 months.
measure: Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity)
timeFrame: Assessed Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Day 1 of every odd cycle, and end of treatment visit, average 12 months
measure: Maximum Concentration of Margetuximab at Steady State
timeFrame: At end of infusion on Cycle 1, Day 1. Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months
measure: Area Under the Concentration Time Curve at Steady State (AUC ss)
timeFrame: Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months
measure: Clearance
timeFrame: Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months.
measure: Volume of Distribution at Steady State
timeFrame: Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .
measure: Terminal Half-life
timeFrame: Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University-Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute/Harvard University Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre - McMaster University
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Daegu
country: Korea, Republic of
facility: Kyungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Raffles Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
References:
citation: Catenacci DVT, Kang YK, Park H, Uronis HE, Lee KW, Ng MCH, Enzinger PC, Park SH, Gold PJ, Lacy J, Hochster HS, Oh SC, Kim YH, Marrone KA, Kelly RJ, Juergens RA, Kim JG, Bendell JC, Alcindor T, Sym SJ, Song EK, Chee CE, Chao Y, Kim S, Lockhart AC, Knutson KL, Yen J, Franovic A, Nordstrom JL, Li D, Wigginton J, Davidson-Moncada JK, Rosales MK, Bang YJ; CP-MGAH22-5 Study Group. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol. 2020 Aug;21(8):1066-1076. doi: 10.1016/S1470-2045(20)30326-0. Epub 2020 Jul 9.