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NCT04164979

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

Active, enrolled Phase 2 Results posted Last updated 11 August 2025
What this trial tests

Phase 2 trial testing Cabozantinib in Gastric Adenocarcinoma in 34 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
4 February 2020
Primary endpoint
25 November 2023
30 May 2026

Quick facts

Lead sponsorUniversity of California, Irvine
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment34
Start date4 February 2020
Primary completion25 November 2023
Estimated completion30 May 2026
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of California, Irvine

Who can join

18 and older, any sex, with Gastric Adenocarcinoma or GastroEsophageal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Progression-free Survival at 6 Months Primary · 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.

GroupValue95% CI
Cabozantinib and Pembrolizumab6
Number of Participants Who Experienced Any Grade 3-5 Adverse Events Secondary · 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.

To evaluate the tolerability of administering cabozantinib in combination with pembrolizumab in patients with advanced gastric and gastroesophageal adenocarcinoma from the start of treatment, duration of treatment and up to 4 weeks after completion of study treatment. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.

GroupValue95% CI
Cabozantinib and Pembrolizumab3
Overall Response Rate as Assessed by RECIST v1.1 Secondary · 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.]

To assess the overall response rate to the combination of cabozantinib and pembrolizumab. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR

GroupValue95% CI
Cabozantinib and Pembrolizumab1
Overall Survival of Patients Who Received Cabozantinib and Pembrolizumab Secondary · From date of registration until death from any cause, whichever came first.

To evaluate overall survival in patients with advanced gastric and gastroesophageal adenocarcinoma treated with this combination of cabozantinib and pembrolizumab.

GroupValue95% CI
Cabozantinib and Pembrolizumab5.53.1 – 14.0

Adverse events — posted to ClinicalTrials.gov

Time frame: 4 years, 2 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cabozantinib and Pembrolizumab
Serious: 3/27 (11%)
Deaths: 23/27

Serious adverse events (3 terms)

ReactionSystemCabozantinib and Pembroliz…
HypertensionVascular disorders
Thromboembolic EventBlood and lymphatic system disorders
Esophageal PerforationGastrointestinal disorders
Other adverse events (10 terms — click to expand)

ReactionSystemCabozantinib and Pembroliz…
FatigueGeneral disorders
AnorexiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
HypothyroidismEndocrine disorders
HypertensionVascular disorders
DysgeusiaNervous system disorders
Muscle CrampsMusculoskeletal and connective tissue disorders
MucositisGastrointestinal disorders
Palmar-Plantar Erythrodysesthesia SyndromeSkin and subcutaneous tissue disorders
Abdominal DistensionGastrointestinal disorders

Most-reported serious reactions: Hypertension, Thromboembolic Event, Esophageal Perforation.

Data from ClinicalTrials.gov NCT04164979 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Gastric cancer immunosuppressive microenvironment heterogeneity: implications for therapy development.
    Yasuda T, Wang YA. · · 2024 · cited 139× · PMID 38600020 · DOI 10.1016/j.trecan.2024.03.008
  2. CAR-T Cell Therapy-An Overview of Targets in Gastric Cancer.
    Bębnowska D, Grywalska E, Niedźwiedzka-Rystwej P, Sosnowska-Pasiarska B, et al · · 2020 · cited 56× · PMID 32560392 · DOI 10.3390/jcm9061894
  3. BDNF and its signaling in cancer.
    Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, et al · · 2023 · cited 48× · PMID 36173463 · DOI 10.1007/s00432-022-04365-8
  4. Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.
    Xia Y, Huang C, Zhong M, Zhong H, et al · · 2025 · cited 32× · PMID 39856684 · DOI 10.1186/s12964-025-02033-1
  5. Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy.
    Petrazzuolo A, Maiuri MC, Zitvogel L, Kroemer G, et al · · 2022 · cited 23× · PMID 35655707 · DOI 10.1080/2162402x.2022.2077898
  6. Overcoming physical stromal barriers to cancer immunotherapy.
    Chung SW, Xie Y, Suk JS. · · 2021 · cited 20× · PMID 34351575 · DOI 10.1007/s13346-021-01036-y
  7. The Role of cMET in Gastric Cancer-A Review of the Literature.
    Van Herpe F, Van Cutsem E. · · 2023 · cited 14× · PMID 37046637 · DOI 10.3390/cancers15071976
  8. Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients.
    Palle J, Hirsch L, Lapeyre-Prost A, Malka D, et al · · 2021 · cited 14× · PMID 34771724 · DOI 10.3390/cancers13215562

Verify or expand the search:

Other trials of Cabozantinib

Trials testing the same drug.

Other recruiting trials for Gastric Adenocarcinoma

Currently open trials in the same condition.

Other University of California, Irvine trials

Trials by the same sponsor.

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