Initial results from the phase 2 LITESPARK-003 (NCT03634540) study showed promising antitumor activity for belzutifan plus cabozantinib as first-line (cohort 1) and subsequent-line (cohort 2) treatment for patients (pts) with advanced ccRCC. We present updated results from cohorts 1 and 2.
Eligible pts had advanced ccRCC and ECOG PS of 0 or 1. Cohort 1 included pts with no prior systemic therapy for advanced RCC. Cohort 2 included pts who had received prior immunotherapy and ≤2 systemic regimens for advanced RCC. All pts received oral belzutifan 120 mg and oral cabozantinib 60 mg once daily. The primary end point was ORR per RECIST v1.1 by investigator assessment. Secondary end points included DOR, PFS, OS, and safety.
A total of 50 pts were enrolled in cohort 1 and 52 pts in cohort 2. Most (n = 28; 56%) pts in cohort 1 had IMDC favorable risk and most (n = 41; 79%) in cohort 2 had IMDC intermediate/poor risk. Median follow-up was 24.3 mo (range, 4.1-48.2) in cohort 1 and 39.8 mo (range, 33.1-55.0) in cohort 2. ORR is shown in the Table. Median DOR was 28.6 mo (range, 1.9+ to 35.8) in cohort 1 and 31.5 mo (range, 4.2+ to 36.8) in cohort 2. An estimated 57% of all responders in cohort 1 and 51% in cohort 2 remained in response for ≥24 mo. Median PFS was 30.3 mo (95% CI, 16-not reached [NR]) in cohort 1 and 13.8 mo (95% CI, 9-19) in cohort 2. Median OS was NR (95% CI, NR-NR) in cohort 1 and 26.7 mo (95% CI, 20-41) in cohort 2. Overall, 23 (46%) pts in cohort 1 and 33 (63%) in cohort 2 had a grade 3-5 treatment-related AE (TRAE). No pts died due to a TRAE in cohort 1 and 1 pt (2%) died due to a TRAE (respiratory failure) in cohort 2.
In this updated analysis of LITESPARK-003, belzutifan plus cabozantinib showed durable antitumor activity and a safety profile consistent with prior observations. These results further support the combination of an HIF-2α inhibitor and VEGFR-TKI as a potential treatment option for advanced ccRCC in both the first- and subsequent-line settings. Table: LBA87
| Cohort 1 | Cohort 2 | |||||
| Total (n = 50) | IMDC favorable (n = 28) | IMDC intermediate/poor (n =22) | Total (n = 52) | IMDC favorable (n = 11) | IMDC intermediate/poor (n = 41) | |
| ORR, % (95% CI) | 70 (55-82) | 79 (59-92) | 59 (36-79) | 31 (19-45) | 27 (6-61) | 32 (18-48) |
| Best overall response, n (%) | ||||||
| CR | 4 (8) | 3 (11) | 1 (5) | 2 (4) | 0 | 2 (5) |
| PR | 31 (62) | 19 (68) | 12 (55) | 14 (27) | 3 (27) | 11 (27) |
| SD | 14 (28) | 6 (21) | 8 (36) | 32 (62) | 8 (73) | 24 (59) |
| PD | 1 (2) | 0 | 1 (5) | 3 (6) | 0 | 3.(7) |
| NA | 0 | 0 | 0 | 1 (2) | 0 | 1 (2) |
NCT03634540, August 16, 2018.