Evidence map›Paper›PMID 41701511›Full record

Trial reportCancer2026

A phase 1b/2 study of cabozantinib in combination with pembrolizumab in advanced cutaneous melanoma.

Yousef Zakharia, Donghyun Kim, Michele Freesmeier, Melanie Frees, Sarah Mott, Varun Monga, Douglas Laux, Asad Javed, John Rieth, John Smestad and 1 more

Abstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yousef ZakhariaDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.
Donghyun KimDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.ORCID https://orcid.org/0009-0005-6998-302X
Michele FreesmeierDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.
Melanie FreesUniversity of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.
Sarah MottUniversity of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.
Varun MongaDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Douglas LauxDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.
Asad JavedDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.
John RiethDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.ORCID https://orcid.org/0000-0002-4883-5301
John SmestadDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.ORCID https://orcid.org/0000-0001-7922-3319
Mohammed MilhemDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa, USA.

Funding

Exelixis IST 59
6 · The paper itself

Abstract

backgroundPembrolizumab is approved for advanced cutaneous melanoma (aCM). Cabozantinib, an oral multi-tyrosine kinase inhibitor, has demonstrated antitumor activity as monotherapy or in combination with anti-PD-1 therapy in malignancies. The objective of this study was to determine the safety and efficacy of cabozantinib and pembrolizumab for patients with aCM.

methodsThis phase 1b/2 study enrolled 28 patients with unresectable aCM. In phase 1b, escalating dose levels of cabozantinib (20 mg, 40 mg, and 60 mg) were administered concurrently with pembrolizumab 200 mg intravenously every 3 weeks using a 3 + 3 design to determine recommended phase 2 dose (RP2D). In phase 2, patients received cabozantinib at RP2D in combination with pembrolizumab using a Simon 2 stage design. Primary end point of phase 2 was overall response rate (ORR). Secondary end points included disease control rate, progression-free survival (PFS), and overall survival (OS).

resultsPhase 1b enrolled eight patients, cabozantinib 40 mg daily dose level was selected as RP2D. Response rate in stage 1 exceeded predefined criteria for proceeding to expansion phase; however, phase 2 was terminated after 20 patients due to low accrual in the setting of evolving standard of care. Among all treated patients, the most common grade ≥3 toxicities were hypertension (n = 10, 36%), hypokalemia (n = 5, 18%), hypophosphatemia (n = 4, 14%), and ALT elevation (n = 4, 14%). Among 20 patients treated in phase 2, ORR was 45%, median PFS was 6.6 months, and median OS was 29.5 months.

conclusionsCabozantinib and pembrolizumab combination was explored in treatment-naive aCM. Toxicity was consistent with known profiles, but discontinuation rates were notable.

Indexed as

AnilidesAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsMelanomaPyridinesSkin NeoplasmsAdultAgedAged, 80 and overCutaneous Malignant MelanomaFemaleHumansMaleMiddle AgedAnilidesAntibodies, Monoclonal, HumanizedcabozantinibpembrolizumabPyridinescombination therapyimmune checkpoint inhibitorskin cancer

Identifiers

PMID41701511
PMCPMC12912253

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.