(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Jesse Zaretsky presented the results of CABIOS, a phase Ib study of cabozantinib and nivolumab in combination with abiraterone in patients with metastatic hormone sensitive prostate cancer (mHSPC).
Androgen deprivation therapy (ADT) in combination with taxanes and/or androgen receptor signaling inhibitors is a standard of care approach for the treatment of mHSPC patients. The combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockade (ICBs) is FDA approved in renal cell carcinoma and shows promising efficacy in preclinical models of prostate cancer by favorably altering the tumor immune microenvironment. There are currently numerous ongoing trials of TKI + ICB in metastatic castration resistant prostate cancer (mCRPC). In this report, Dr. Zaretsky presented the results of CABIOS (NCT04477512), an ongoing phase Ib single-arm trial of combination cabozantinib, nivolumab, and abiraterone/prednisone in patients with newly diagnosed mHSPC.
CABIOS included patients with de novo or recurrent mHSPC with an ECOG performance status of 0-1 and adequate organ function. Patients were allowed 12 weeks of ADT prior to enrollment, but no prior abiraterone or docetaxel use was permitted. Patients received cabozantinib 20 mg or 40 mg daily (3+3 dose escalation in two cohorts) combined with nivolumab 480mg IV every 4 weeks, and abiraterone/prednisone at a dose of 1,000mg/5mg daily until progression or unacceptable toxicity.
The primary endpoint was safety and tolerability. Secondary endpoints included overall response rate (ORR) by RECIST 1.1, overall survival (OS), progression-free survival (PFS), and PSA response. Exploratory analyses included mass cytometry or Cytometry by Time of Flight (CyTOF) of peripheral blood and serum cytokine ELISA.
As of December 19, 2022, 17 patients were enrolled (cabozantinib 20 mg: 3 patients; cabozantinib 40 mg: 14 patients). No dose-limiting toxicities were observed. The median patient age was 65 years and 4/17 (25%) were African American or Black. 11/17 patients had de novo disease, with the remaining 6 having recurrent mHSPC. The median baseline serum PSA was 78 ng/mL. The most frequent site of metastasis was bone (n=16), followed by lymph node (n=6) and lungs (n=1). 11/17 patients (65%) had high-volume disease.
At a median follow-up of 12.8 months, 9 patients (53%) remained on study. One patient withdrew consent, 3 discontinued due to disease progression (with 1 death), and 4 stopped treatment due to toxicity. Grade ≥ 3 adverse events included:
- Elevated AST/ALT (n=4)
- Diarrhea (n=2)
- Encephalitis (n=1, grade 4 likely nivolumab-related after one year on therapy)
- Wound infection/dehiscence (n=1)
- Adrenal insufficiency (n=1)
- Hypertension (n=1)
- Elevated lipase (n=1)
- Proteinuria (n=1)
No other adverse events were reported outside the current safety labels for the study agents. Of 15 response evaluable patients, 7 had RECIST-measurable lesions; 4 had partial response and 3 had stable disease as best response at data cutoff. 9/14 (64.3%) evaluable patients had a PSA <0.2 ng/mL at 7 months. The immune correlative studies are ongoing.
In summary, CABIOS is the first trial evaluating the combination of cabozantinib and nivolumab in mHSPC patients receiving abiraterone. This combination appears to have a safety profile consistent with known adverse events for these agents, no dose-limiting toxicities, and evidence of clinical benefit. Further follow up will be required to fully assess the clinical safety, efficacy, and immune responses. Dr. Zaretsky suggested that future, larger studies could compare this combination to standard of care ADT + abiraterone.
Presented by: Jesse Meir Zaretsky, MD, PhD, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.