Ph II Study of Cabozantinib With Pembrolizumab in Metastatic Gastric and Gastroesophageal Adenocarcinoma

NCT04164979 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20195426UCI 18-124
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 single-arm, open-label clinical trial determining efficacy of cabozantinib in combination with pembrolizumab in subjects with advanced gastric and gastroesophageal adenocarcinoma. These are subjects who have progressed, or not tolerated, at least one prior line of chemotherapy with a fluoropyrimidine and platinum agent.

Conditions

Gastric Adenocarcinoma; GastroEsophageal Cancer

Keywords

Gastric Adenocarcinoma; Gastroesophageal Adenocarcinoma; Cabozantinib; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-free Survival at 6 Months

  This is defined as the percentage of subjects who are free of progression 6 months after study treatment start. Progression is defined death, radiographic progression or clinical deterioration attributed disease progression as judged by an investigator. Radiographic progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm and/or appearance of new lesions.

  6 Months

Secondary Outcomes (3)

• Number of Participants Who Experienced Any Grade 3-5 Adverse Events

  From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

• Overall Response Rate as Assessed by RECIST v1.1

  From date of registration until first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.]

• Overall Survival of Patients Who Received Cabozantinib and Pembrolizumab

  From date of registration until death from any cause, whichever came first.

Study Arms (1)

Cabozantinib and Pembrolizumab

EXPERIMENTAL

Subjects receive Cabozantinib 40mg PO daily on days 1-21 and Pembrolizumab 200mg IV on day 1 every 21 days.

Drug: Cabozantinib; Drug: Pembrolizumab

Interventions

Cabozantinib DRUG

Given PO

Also known as: CABOMETYX, COMETRIQ

Cabozantinib and Pembrolizumab

Pembrolizumab DRUG

Given IV

Also known as: KEYTRUDA

Cabozantinib and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed gastric or gastroesophageal adenocarcinoma
• Must have locally advanced, recurrent, or metastatic disease not amenable to curative intent surgery.
• Must have progressed, or not tolerated, at least one line of treatment with a platinum and/or fluoropyrimidine containing regimen. At least one cycle of combination chemotherapy including a platinum (oxaliplatin, cisplatin, carboplatin) and/or fluoropyrimidine (capecitabine or 5-Fluorouracil) based regimen for advanced disease. Combination regimens with platinum/fluoropyrimidine containing a taxane and or a checkpoint inhibitor are allowed. Patients progressing within six months of perioperative chemotherapy or definitive chemoradiation for localized disease are eligible. Patients who have exhausted all other standard of care options are also eligible.
• Must have received and progressed on one previous line of treatment containing a checkpoint inhibitor (if PD-L1 Combined Positive Score (CPS) score unknown or ≥ 10%). Patients with PD-L1 CPS score \< 10% are eligible independent of whether they have received previous checkpoint inhibitors.
• Age ≥ 18 years
• Performance status: Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Life expectancy of greater than 3 months
• Adequate organ and marrow function as defined below:
• Leukocytes: ≥ 2,000/mcL
• absolute neutrophil count: ≥ 1000/mcL
• platelets: ≥ 60,000/mcl
• total bilirubin: within normal institutional limits (or \<3mg/dL in patients with Gilbert's disease)
• AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present
• creatinine: \< 1.5 X upper limit of normal
• hemoglobin: ≥ 8 g/dL

You may not qualify if:

• Patients who have had chemotherapy within 2 weeks prior to entering the study
• All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases or cranial epidural disease unless accurately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. These individuals should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, cabozantinib or other agents used in study. Patients with documented previous immune related toxicities which led to discontinuation of a checkpoint inhibitor.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors betrixaban, or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
• Uncontrolled intercurrent illness including, but not limited to, the following conditions:
• ongoing or active infection
• symptomatic congestive heart failure
• uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose
• unstable angina pectoris

Sponsors & Collaborators

• University of California, Irvine: lead
• Exelixis: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

Related Publications (1)

• Dayyani F, Chao J, Lee FC, Taylor TH, Neumann K, Cho MT. A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors. Oncologist. 2024 Aug 5;29(8):721-e1088. doi: 10.1093/oncolo/oyae117.

  PMID: 38823034 DERIVED

MeSH Terms

Interventions

cabozantinib; pembrolizumab

Results Point of Contact

• Title: Chao Family Comprehensive Cancer Center, University of California, Irvine
• Organization: Chao Family Comprehensive Cancer Center, University of California, Irvine

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• Farshid Dayyani, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 15, 2019
• Study Start: February 4, 2020
• Primary Completion: November 25, 2023
• Study Completion: May 30, 2026
• Last Updated: August 11, 2025
• Results First Posted: August 11, 2025

Record last verified: 2025-07

Locations

US (1)