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662 Phase I/II study of ipilimumab plus nivolumab combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma
  1. Rohit Jain1,
  2. Yuanquan Yang2,
  3. Juskaran Chadha1,
  4. Monica Chatwal1,
  5. Sarah Raymond1,
  6. Erika Saunders1,
  7. Trey Poehlman1,
  8. Wenyi Fan1,
  9. Youngchul Kim1,
  10. Jasreman Dhillon1,
  11. Amir Mortazavi3,
  12. Jingsong Zhang1 and
  13. Guru P Sonpavde4
  1. 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
  2. 2The Ohio State University/Pelotonia Institute for Immuno-Oncology, Columbus, OH, USA
  3. 3The Ohio State University, Columbus, OH, USA
  4. 4Advent Health Cancer Institute, Orlando, FL, USA


Background Sacituzumab govitecan (SG) demonstrated an ORR of 27% and median OS of 10.5 months (Mo) in metastatic urothelial carcinoma (mUC) patients (pts) progressing after platinum chemotherapy and PD1/L1 inhibitor. The combination of SG and pembrolizumab is safe and active following platinum chemotherapy. Ipilimumab (IPI) 3mg/kg plus Nivolumab (NIVO) 1mg/kg (I3+N1) has shown promising activity in post-platinum mUC pts. Given the potential synergism between immunogenic cell death induced by SG and IPI-NIVO, we hypothesized that the combination of SG and IPI-NIVO would be safe and active as a frontline treatment for cisplatin ineligible mUC.

Methods 3+ 3 design was used for the phase I dose escalation of SG at 8 mg/kg and 10 mg/kg dose levels. I3+N1 was given IV every 3 weeks x 4 cycles followed by NIVO 360 mg IV day 1 every 3 weeks. SG was given IV at days 1,8 every 3 weeks The primary endpoint was safety and recommended phase 2 dose (RP2D) based on dose limiting toxicity (DLTs) observed in cycle 1; key secondary endpoints include ORR, DOR, PFS and OS. Key inclusion criteria were ECOG-PS 0–1, cisplatin-ineligibility, treatment naïve, no prior PD1/L1 inhibitor except >3 months earlier for localized disease.

Results The study has completed phase I dose escalation after enrolling a total of 9 patients (8 men, 1-woman, median age: 74 years). Six patients were enrolled at SG 8 mg/kg with 1 DLT, and 3 patients at 10 mg/kg with 2 DLTs. DLTs included grade 3 skin rash (n=2) and grade 3 pneumonitis (n=1). The RP2D of SG was determined to be 8 mg/kg with I3+N1. The most common treatment-related adverse events (TRAE) included anemia (66.6%) neutropenia (66.6%), pruritus (66.6%), fatigue (66.6%), and diarrhea (66.6%). 2 patients developed grade 2 infusion reactions to SG. Other grade ≥ 3 TRAE included neutropenia (55.5%), anemia (33.3%), arthralgia (11.1%), and elevated amylase/lipase (11.1%). Of the 9 patients, 6 patients were considered evaluable for response of whom 4 had partial response (ORR 66.6%). With the median follow-up time of 18.8 Mo (95% CI 14.8-NR), the median DOR was 10.7 Mo (range 4.6–12.0); mPFS was 8.78 Mo (95% CI 3.8-NR) and mOS was NR.

Conclusions The RP2D of SG was identified as 8mg/kg in combination with I3+N1 as first-line therapy for cisplatin-ineligible mUC. Early signals of promising activity were observed in a small cohort of evaluable pts. The Phase 2 trial is ongoing coupled with exploratory biomarker analyses. NCT04863885

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