NCT03957551 is a Phase 1, PHASE2 clinical trial of Cabozantinib in Advanced Metastatic Melanoma, sponsored by John Rieth.

Who is sponsoring NCT03957551?

NCT03957551 is sponsored by John Rieth.

What drugs are being tested in NCT03957551?

Interventions in NCT03957551: Cabozantinib, Pembrolizumab.

What condition does NCT03957551 study?

NCT03957551 studies Advanced Metastatic Melanoma.

Is NCT03957551 still recruiting?

NCT03957551 is currently terminated. Last updated 29 January 2026.

Are results published for NCT03957551?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2026-01-29 · How we verify

NCT03957551

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Cabozantinib and Pembrolizumab for Advanced Metastatic Melanoma

Terminated Phase 1, PHASE2 Results posted Last updated 29 January 2026

What this trial tests

Phase 1, PHASE2 trial testing Cabozantinib in Advanced Metastatic Melanoma in 28 participants. Terminated before completion.

Timeline

27 August 2019

Primary endpoint
10 June 2024

17 October 2025

Quick facts

Lead sponsor	John Rieth
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	28
Start date	27 August 2019
Primary completion	10 June 2024
Estimated completion	17 October 2025
Sites	1 location across United States

Drugs / interventions tested

Cabozantinib (CABOZANTINIB) — full drug profile →
Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

Advanced Metastatic Melanoma — all drugs for Advanced Metastatic Melanoma →

Sponsor

John Rieth

Who can join

18 and older, any sex, with Advanced Metastatic Melanoma. 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.

Phase I: Number of Participants With a Dose Limiting Toxicity (DLT) Using CTCAE, Version 4.03 Primary · Up to 21 days

All adverse events (AEs) will be considered in DLT assessment unless an event is clearly unrelated to trial treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 will be used.

Group	Value	95% CI
Phase I: Cabozantinib and Pembrolizumab (40mg)	1
Phase I: Cabozantinib and Pembrolizumab (60mg)	0

Phase II: Overall Response Rate Primary · Initiation of treatment up to 2 years

The overall response rate (ORR) is the percentage of patients with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). A complete response (CR) is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm, and partial response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions.

Group	Value	95% CI
Phase II: Cabozantinib and Pembrolizumab	9

Disease Control Rate Secondary · Initiation of treatment up to 2 years

The disease control rate (DCR) is the percentage of patients with a complete response (CR), partial response (PR) or stable disease (SD) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). A complete response (CR) is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm, partial response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions, and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

Group	Value	95% CI
Phase II: Cabozantinib and Pembrolizumab	15

Progression-Free Survival Secondary · Initiation of treatment up to 2 years

Progression-free survival (PFS) is defined as the time from study treatment initiation to the date of first documentation of disease progression or death due to any cause. Otherwise, patients were censored at date of last radiographic assessment.

Group	Value	95% CI
Phase II: Cabozantinib and Pembrolizumab	6.6	2.9 – 29.5

Overall Survival at 2 Years Secondary · Initiation of treatment up to 2 years

Overall survival (OS) is defined as the time from study treatment initiation to death due to any cause. Patients still alive were censored at the last date known to be alive. Cumulative OS was descriptively summarized over time with the Kaplan-Meier method. The landmark estimate at 2 years and associated 95% confidence interval is reported.

Group	Value	95% CI
Phase II: Cabozantinib and Pembrolizumab	63	37 – 80

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs were collected from the time of signing informed consent through 30 days after the last dose of cabozantinib and/or pembrolizumab treatment, up to 2 years.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I: Cabozantinib and Pembrolizumab (40mg)

Serious: 0/6 (0%)

Deaths: 2/6

Phase I: Cabozantinib and Pembrolizumab (60mg)

Serious: 1/2 (50%)

Deaths: 1/2

Phase II: Cabozantinib and Pembrolizumab (40mg)

Serious: 7/20 (35%)

Deaths: 10/20

Serious adverse events (12 terms)

Reaction	System	Phase I: Cabozantinib and …	Phase I: Cabozantinib and …	Phase II: Cabozantinib and…
Myocarditis	Cardiac disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—
Small intestinal perforation	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Death NOS	General disorders and administration site conditions	—	—	—
Pain	General disorders and administration site conditions	—	—	—
Blood bilirubin increased	Investigations	—	—	—
Nervous system disorders - Other, specify	Nervous system disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Hypotension	Vascular disorders	—	—	—
Vascular disorders - Other, specify	Vascular disorders	—	—	—

Other adverse events (121 terms — click to expand)

Reaction	System	Phase I: Cabozantinib and …	Phase I: Cabozantinib and …	Phase II: Cabozantinib and…
Fatigue	General disorders and administration site conditions	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Hyperthyroidism	Endocrine disorders	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Urine discoloration	Renal and urinary disorders	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
GGT increased	Investigations	—	—	—
Lymphocyte count decreased	Investigations	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Hematuria	Renal and urinary disorders	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—
Weight loss	Investigations	—	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Mucositis oral	Gastrointestinal disorders	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—
Neutrophil count decreased	Investigations	—	—	—
Hyperkalemia	Metabolism and nutrition disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Fever	General disorders and administration site conditions	—	—	—
General disorders and administration site conditions - Other, specify	General disorders and administration site conditions	—	—	—
Pain	General disorders and administration site conditions	—	—	—
Blood bilirubin increased	Investigations	—	—	—

Most-reported serious reactions: Myocarditis, Abdominal pain, Dysphagia, Small intestinal perforation, Vomiting, Death NOS, Pain, Blood bilirubin increased.

Data from ClinicalTrials.gov NCT03957551 adverse events section.

Sponsor's own description

The study aims to evaluate the safety and preliminary efficacy of the combination of cabozantinib and pembrolizumab in advanced melanoma

Publications & conference data

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

Current Advances in the Treatment of BRAF-Mutant Melanoma.
Patel H, Yacoub N, Mishra R, White A, et al · · 2020 · cited 133× · PMID 32092958 · DOI 10.3390/cancers12020482
BRAF Gene and Melanoma: Back to the Future.
Ottaviano M, Giunta EF, Tortora M, Curvietto M, et al · · 2021 · cited 75× · PMID 33801689 · DOI 10.3390/ijms22073474
Hypoxia-dependent drivers of melanoma progression.
D'Aguanno S, Mallone F, Marenco M, Del Bufalo D, et al · · 2021 · cited 67× · PMID 33964953 · DOI 10.1186/s13046-021-01926-6
Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness.
Barnestein R, Galland L, Kalfeist L, Ghiringhelli F, et al · · 2022 · cited 66× · PMID 36117524 · DOI 10.1080/2162402x.2022.2120676
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
Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review.
Gao L, Yang X, Yi C, Zhu H. · · 2019 · cited 42× · PMID 31680957 · DOI 10.3389/fphar.2019.01173
RTK Inhibitors in Melanoma: From Bench to Bedside.
Sabbah M, Najem A, Krayem M, Awada A, et al · · 2021 · cited 38× · PMID 33918490 · DOI 10.3390/cancers13071685
Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.
Rager T, Eckburg A, Patel M, Qiu R, et al · · 2022 · cited 34× · PMID 35954441 · DOI 10.3390/cancers14153779

Verify or expand the search:

Other trials of Cabozantinib

Trials testing the same drug.

NCT07383441 — Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer · Phase 3 · not yet recruiting
NCT07293351 — A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Ipilimumab or Caboz · Phase 1, PHASE2 · recruiting
NCT07187869 — Modulation of the Bone Immune Microenvironment Following Cabozantinib Treatment of Bone Metastatic Clear Cell Renal Cell · Phase 1 · not yet recruiting
NCT07405164 — Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043) · Phase 3 · recruiting
NCT06900595 — Testing the Addition of an Anti-Cancer Drug, Cabozantinib to the Immunotherapy Drug Cemiplimab (REGN2810), in Adolescent · Phase 2 · recruiting

Other John Rieth trials

Trials by the same sponsor.

NCT06660810 — Neoadjuvant Intralesional Injection of Talimogene Laherparepvec · Phase 2 · active not recruiting
NCT04599062 — TVEC and Preop Radiation for Sarcoma (8 ml Dose) · Phase 1, PHASE2 · active not recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03957551 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by John Rieth
Last refreshed: 29 January 2026

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03957551.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing