A Phase I/II Study of Rovalpituzumab Tesirine in Combination With Nivolumab ± Ipilimumab in Patients With Previously Treated Extensive-Stage Small Cell Lung Cancer.

Abstract Introduction This open-label, phase I/II study assessed safety and efficacy of rovalpituzumab tesirine (Rova-T™), an antibody-drug conjugate targeting delta-like protein 3 plus immune checkpoint inhibitors nivolumab ± ipilimumab in previously treated extensive-stage small cell lung cancer (ES SCLC). Methods Patients with histologically/cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 weeks for two cycles) plus 360 mg nivolumab (two 3-week cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as Cohort 1 plus 1 mg/kg nivolumab (four 3-week cycles) and 1 mg/kg ipilimumab (beginning week 4). Both cohorts received 480 mg nivolumab every 4 weeks starting at week 10.Key objectives were to assess safety/tolerability and efficacy (per RECIST v1.1). The response-related results are based on centrally read data. Results Forty-two patients received therapy: cohort 1, n=30; cohort 2, n=12. Overall, 43% received two or more prior lines of therapy. All patients experienced one or more treatment-emergent adverse event (TEAE); 41 patients reported AEs considered related to study drug by the investigator. The most frequent TEAE was pleural effusion (n=20, 48%); most common grade ≥3 was anemia (n=9, 21%). Three grade 5 TEAEs considered related to study drug were reported (cohort 1): pneumonitis (n=2), acute kidney injury (n=1). The objective response rate was 30% (12/40): cohort 1, 27.6% (8/29); cohort 2, 36.4% (4/11); all partial responses. Conclusions Despite encouraging antitumor activity in previously treated ES SCLC, combination therapy with Rova-T and nivolumab ± ipilimumab was not well tolerated at the dose levels and administration schedules evaluated.