ArticleJournal for immunotherapy of cancer2022
Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02298959 (A Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients With Advanced Solid Tumors), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
A Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients With Advanced Solid Tumors
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.The oncologist · 2024Pooled it
- Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914).Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Bifidobacterium breve inhibits colorectal cancer via extracellular vesicles containing formate acetyltransferase.Journal of nanobiotechnology · 2026Article
- Unraveling vascular mechanisms in melanoma: roles of angiogenesis and vasculogenic mimicry in tumor progression and therapeutic resistance.Cancer biology & medicine · 2025Review
- Review
- Focus on PD-1/PD-L1-Targeting Antibodies in Colorectal Cancer: Are There Options Beyond Dostarlimab, Nivolumab, and Pembrolizumab? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.Current treatment options in oncology · 2025Review
- Melanoma-derived extracellular vesicles transfer proangiogenic factors.Oncology research · 2025Review
- Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma.Cell discovery · 2024Article
- Review
- Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment.Cancer immunology, immunotherapy : CII · 2024Article
- Article
- Vascular normalization: reshaping the tumor microenvironment and augmenting antitumor immunity for ovarian cancer.Frontiers in immunology · 2023Review
- Evaluation of immunotherapy efficacy in gynecologic cancer.Frontiers in immunology · 2023Review
- The roles of TGF-β and VEGF pathways in the suppression of antitumor immunity in melanoma and other solid tumors.Pharmacology & therapeutics · 2022Review
- Prediction of immunotherapy efficacy and immunomodulatory role of hypoxia in colorectal cancer.Therapeutic advances in medical oncology · 2022Review
- The role of angiogenesis in melanoma: Clinical treatments and future expectations.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundThe combination of antiangiogenic agents with immune checkpoint inhibitors could potentially overcome immune suppression driven by tumor angiogenesis. We report results from a phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors.
methodsThis is a multicenter phase IB dose-escalation study of the combination of ziv-aflibercept (at 2-4 mg/kg) plus pembrolizumab (at 2 mg/kg) administered intravenously every 2 weeks with expansion cohorts in programmed cell death protein 1 (PD-1)/programmed death-ligand 1(PD-L1)-naïve melanoma, renal cell carcinoma (RCC), microsatellite stable colorectal cancer (CRC), and ovarian cancer. The primary objective was to determine maximum tolerated dose (MTD) and recommended dose of the combination. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Exploratory objectives included correlation of clinical efficacy with tumor and peripheral immune population densities.
resultsOverall, 33 patients were enrolled during dose escalation (n=3) and dose expansion (n=30). No dose-limiting toxicities were reported in the initial dose level. Ziv-aflibercept 4 mg/kg plus pembrolizumab 2 mg/kg every 2 weeks was established as the MTD. Grade ≥3 adverse events occurred in 19/33 patients (58%), the most common being hypertension (36%) and proteinuria (18%). ORR in the dose-expansion cohort was 16.7% (5/30, 90% CI 7% to 32%). Complete responses occurred in melanoma (n=2); partial responses occurred in RCC (n=1), mesothelioma (n=1), and melanoma (n=1). Median OS was as follows: melanoma, not reached (NR); RCC, 15.7 months (90% CI 2.5 to 15.7); CRC, 3.3 months (90% CI 0.6 to 3.4); ovarian, 12.5 months (90% CI 3.8 to 13.6); other solid tumors, NR. Activated tumor-infiltrating CD8 T cells at baseline (CD8+PD1+), high CD40L expression, and increased peripheral memory CD8 T cells correlated with clinical response.
conclusionThe combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma. TRIAL REGISTRATION NUMBER: NCT02298959.
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Registered trials
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 OpenQuestion graph.