Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer

MacroGenics95 enrolled

Overview

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: 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastric Cancer Stomach Cancer Esophageal Cancer

Interventions

Margetuximab 10 mg/kgBIOLOGICAL

Margetuximab treatment is administered intravenously (IV) once every 21-day cycle

Margetuximab 15 mgBIOLOGICAL

Margetuximab treatment is administered IV once every 21-day cycle

PembrolizumabBIOLOGICAL

Pembrolizumab treatment is administered IV once every 21-day cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (28)

Outcomes

Primary Outcomes

Number of Patients With Dose Limiting Toxicities

Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab when administered in combination with pembrolizumab

Time frame: 21 days

Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).

The number of patients that experience either an AE or a SAE during the study participation

Time frame: up to 24 months

Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment

Investigate the preliminary anti-tumor activity as measured by response to treatment of margetuximab when administered in combination with pembrolizumab, using conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Time frame: 12 months

Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria

Investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR) of margetuximab when administered in combination with pembrolizumab, using immune-related response criteria (irRC).

Time frame: 12 Months

Duration of Response

Duration of response is calculated at the time from CR or PR to relapse or cancer progression.

Time frame: up to 24 months

Secondary Outcomes

Overall Survival (OS)

The median length of time between first dose of study medication and death from any cause.

Time frame: 24 Months

Progression Free Survival (PFS)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.