KEY TAKEAWAYS
- The MAIN-CAV trial is a phase III randomized, multicenter, international trial for locally advanced/mUC pts.
- The trial’s primary aim is to determine if adding the multitargeted TKI, CABO, to Av leads to improved clinical outcomes compared to Av alone.
- 654 adult pts will be randomized 1:1 within 3-10 weeks after the last dose of chemotherapy to receive Av or a combination of Av and CABO for up to 2 yrs.
- The primary endpoint is overall survival with critical secondary endpoints including progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors.
- (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs. avelumab alone.
Patients (pts) with mUC who do not progress after first-line platinum-based chemotherapy should receive maintenance avelumab (Av). Combining Av with a practical, non-cross-resistant therapy with non-overlapping toxicity would further improve outcomes, but this need is not currently being met. Combining PD-1/PD-1L1 inhibitors and the oral MET, VEGFR, and TAM family receptor inhibitor cabozantinib (CABO) effectively treats UC. Researchers hypothesize that the coordination between CABO and Av will improve the benefit of Av maintenance in mUC in patients with an acceptable safety profile. Patients with locally advanced/mUC (including N3-only disease) who have not progressed after 4-6 cycles of any platinum-based chemotherapy are eligible to participate in MAIN-CAV, a phase III randomized, multicenter, international trial (gem-cis, gem-carbo, MVAC or ddMVAC).
654 adult pts will be randomly assigned to receive either Av 800 mg IV every 2 wk or a combination of Av and CABO 40 mg orally daily for up to 2 yrs., between 3 and 10 weeks (wk) after their last dose of chemotherapy. Essential criteria for eligibility include an ECOG Performance Status (PS) of 0-1; no history of immunotherapy (except BCG); no evidence of central nervous system metastases; no history of major surgery within four weeks; and no uncontrolled hypertension or cardiovascular disorders. Patients (Pts) will be divided into groups based on two factors: 1) whether they had a complete response, partial response, or stable disease to 1L therapy, and 2) whether or not they had visceral metastases. With a one-sided alpha of 0.025, 80% power, a median overall survival (OS) of 21 months (mo) on the Av arm, and a hazard ratio (HR) of 0.75, Researchers can hypothesize that the median OS in the CABO-Av combination arm will be 28 months.
Progression-free survival, safety, tolerability, and activity of CABO-Av relative to Av alone, according to RECIST 1.1 and iRECIST criteria, and PD-L1 status of pts’ tumors are critical secondary endpoints. Patients on CABO-avelumab will be compared to those on avelumab alone regarding their quality of life (QOL) using the EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, and EORTC QLQ-BLM30. Baseline and serial blood, ctDNA, stool, urine samples, and archival tissues collected at baseline will be used to analyze biomarkers of response and resistance to Av. Imaging research will incorporate radiologic and biologic features to predict outcomes and test the correlation of established and new radiomic signatures with OS, adverse events, and QOL. Adding the multitargeted TKI, CABO, to Av in a randomized controlled trial would be the first time that question had been systematically investigated. U10CA180821, U10CA180882, U24CA196171, and U10CA180863 have my full backing (CCTG).
Source: https://meetings.asco.org/abstracts-presentations/213289
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT05092958
Shilpa Gupta, Karla V. Ballman, Matt D. Galsky, Michael J. Morris, Ronald C. Chen, Timothy A. Chan, Laurent Dercle, Yujia Wen, Srikala S. Sridhar, Aihua Edward Yen, Petros Grivas, Alan Tan, Shiva Baghaie, Jonathan E. Rosenberg/MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients with metastatic urothelial cancer (mUC) (Alliance A032001)/J Clin Oncol 40, 2022 (suppl 16; abstr TPS4607)DOI10.1200/JCO.2022.40.16_suppl.TPS4607.
