Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study - 03/05/23
, David F McDermott, MD b, Jaime Merchan, MD c, Todd M Bauer, MD d, Robert Figlin, MD e, Elisabeth I Heath, MD f, M Dror Michaelson, MD g, Edward Arrowsmith, MD h, Anishka D’Souza, MD i, Song Zhao, MD PhD j, Ananya Roy, PhD k, Rodolfo Perini, MD k, Donna Vickery, MD k, Scott S Tykodi, MD PhD lSummary |
Background |
Few treatment options are available for patients with advanced renal cell carcinoma who have received previous anti-PD-1-based or anti-PD-L1-based immunotherapy. Combining belzutifan, an HIF-2α inhibitor, with cabozantinib, a multitargeted tyrosine-kinase inhibitor of VEGFR, c-MET, and AXL, might provide more antitumoural effects than either agent alone. We aimed to investigate the antitumour activity and safety of belzutifan plus cabozantinib in patients with advanced clear cell renal cell carcinoma that was previously treated with immunotherapy.
Methods |
This open-label, single-arm, phase 2 study was conducted at ten hospitals and cancer centres in the USA. Patients were enrolled into two cohorts. Patients in cohort 1 had treatment-naive disease (results will be reported separately). In cohort 2, eligible patients were aged 18 years or older with locally advanced or metastatic clear cell renal cell carcinoma, measurable disease according to Response Evaluation Criteria in Solid Tumours version 1.1, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and had previously received immunotherapy and up to two systemic treatment regimens. Patients were given belzutifan 120 mg orally once daily and cabozantinib 60 mg orally once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint was confirmed objective response assessed by the investigator. Antitumour activity and safety were assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03634540, and is ongoing.
Findings |
Between Sept 27, 2018, and July 14, 2020, 117 patients were screened for eligibility, 52 (44%) of whom were enrolled in cohort 2 and received at least one dose of study treatment. Median age was 63·0 years (IQR 57·5–68·5), 38 (73%) of 52 patients were male, 14 (27%) were female, 48 (92%) were White, two (4%) were Black or African American, and two were Asian (4%). As of data cutoff (Feb 1, 2022), median follow-up was 24·6 months (IQR 22·1–32·2). 16 (30·8% [95% CI 18·7–45·1]) of 52 patients had a confirmed objective response, including one (2%) who had a complete response and 15 (29%) who had partial responses. The most common grade 3–4 treatment-related adverse event was hypertension (14 [27%] of 52 patients). Serious treatment-related adverse events occurred in 15 (29%) patients. One death was considered treatment related by the investigator (respiratory failure).
Interpretation |
Belzutifan plus cabozantinib has promising antitumour activity in patients with pretreated clear cell renal cell carcinoma and our findings provide rationale for further randomised trials with belzutifan in combination with a VEGFR tyrosine-kinase inhibitor.
Funding |
Merck Sharp & Dohme (a subsidiary of Merck & Co) and the National Cancer Institute.
El texto completo de este artículo está disponible en PDF.Esquema
Vol 24 - N° 5
P. 553-562 - mai 2023 Regresar al número
Artículo precedente
- Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial
- Peter Hillmen, Alexandra Pitchford, Adrian Bloor, Angus Broom, Moya Young, Ben Kennedy, Renata Walewska, Michelle Furtado, Gavin Preston, Jeffrey R Neilson, Nicholas Pemberton, Gamal Sidra, Nicholas Morley, Kate Cwynarski, Anna Schuh, Francesco Forconi, Nagah Elmusharaf, Shankara Paneesha, Christopher P Fox, Dena R Howard, Anna Hockaday, Julia M Brown, David A Cairns, Sharon Jackson, Natasha Greatorex, Nichola Webster, Jane Shingles, Surita Dalal, Piers E M Patten, David Allsup, Andrew Rawstron, Talha Munir
- Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa
- Kadia Petricca, Joyce Kambugu, Jessie Githang’a, William M Macharia, Festus Njuguna, Angela McLigeyo, Mary Nyangasi, Jackson Orem, Aimable Kanyamuhunga, Rehema Laiti, Deogratias Katabalo, Kristin Schroeder, Khama Rogo, Bryan Maguire, Lucy Wambui, Jean N Nkurunziza, Bryan Wong, Joshua Neposlan, Lilian Kilawe, Sumit Gupta, Avram E Denburg
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
¿Ya suscrito a @@106933@@ revista ?