Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma Journal Article
| Authors: | Beckermann, K. E.; Shah, N. J.; Campbell, M. T.; Haas, N. B.; Nelson, A.; Ornstein, M. C.; Mao, S.; Keshava-Prasad, H. S.; Hammers, H.; Gao, X.; Gourdin, T.; George, S.; Hoimes, C. J.; Hussain, A.; Jonasch, E.; Rini, B. I.; Voss, M. H. |
| Article Title: | Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma |
| Abstract: | Background: Anexelokto (AXL) protein and its ligand, growth arrest specific-6 (GAS6), are important drivers of metastasis in patients with advanced clear cell renal cell carcinoma (ccRCC). Batiraxcept competitively binds GAS6 limiting interaction with AXL and thereby reduces down¬stream signaling. We present the safety and efficacy of batiraxcept alone and in combination with cabozantinib with or without nivolumab in patients with advanced ccRCC. Patients and methods: Phase 1b tested batiraxcept (15 and 20 mg/kg) plus cabozantinib (60 mg, N = 26) to identify the recommended phase 2 dose (RP2D) and evaluate safety. Phase 2 tested the batiraxcept RP2D as monotherapy (N = 10), as doublet therapy with cabozantinib (60 mg, N = 25) in previously treated patients, and as triplet therapy with cabozantinib (40 mg) and nivolumab (240 or 480 mg) in treatment-naïve patients (N = 11), with objective response rate (ORR) as the primary endpoint. Results: During the phase 1b (N = 26) study portion, no dose-limiting treatment-related adverse events (trAEs) were noted and batiraxcept 15 mg/kg plus cabozantinib 60mg was selected as the RP2D. The ORR across all doublet patients (phase 1 and 2, n = 51) was 43%, with median PFS of 9.2 months and grade 33 trAEs in 73% of patients. Common batiraxcept trAEs were diarrhea (31%), fatigue (31%), and infu¬sion reactions (24%). No new safety signals were noted among the triplet or monotherapy arms, which demonstrated 54% and 0% ORR, respectively. Conclusion: Batiraxcept was well tolerated with promising early efficacy signal when combined with cabozantinib, especially in heavily pre¬treated patients with ccRCC. The trial was discontinued early due to the sponsor's internal decision. © 2025 The Author(s). Published by Oxford University Press. |
| Keywords: | adult; treatment response; aged; aged, 80 and over; middle aged; major clinical study; clinical trial; fatigue; advanced cancer; diarrhea; drug efficacy; drug safety; pyridines; antineoplastic agent; anorexia; progression free survival; phase 2 clinical trial; anemia; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; cohort analysis; pathology; risk factor; histology; renal cell carcinoma; kidney neoplasms; drug dose escalation; alkaline phosphatase; recombinant fusion proteins; kidney tumor; carcinoma, renal cell; phase 1 clinical trial; kidney cancer; drug therapy; hand foot syndrome; electrocardiography; anilides; axl receptor tyrosine kinase; oral mucositis; dysgeusia; pyridine derivative; anilide; clear cell renal cell carcinoma; refractory; fusion protein; hypertransaminasemia; Common Terminology Criteria for Adverse Events; cabozantinib; nivolumab; infusion related reaction; very elderly; humans; human; male; female; article; tyrosine kinase inhibitor (tki); ecog performance status; hyperphosphatasemia; batiraxcept |
| Journal Title: | The Oncologist |
| Volume: | 30 |
| Issue: | 6 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-06-01 |
| Start Page: | oyaf138 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyaf138 |
| PUBMED: | 40549043 |
| PROVIDER: | scopus |
| PMCID: | PMC12205982 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Neil J. Shah -- Source: Scopus |
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