A Phase 1-2 Study of Rovalpituzumab Tesirine in Combination With Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Extensive-Stage SCLC

Jyoti Malhotra, Petros Nikolinakos, Ticiana Leal, Jonathan Lehman, Daniel Morgensztern, Jyoti D Patel, John M Wrangle, Giuseppe Curigliano, Laurent Greillier, Melissa L Johnson, Neal Ready, Gilles Robinet, Satwant Lally, David Maag, Ricardo Valenzuela, Vincent Blot, Benjamin Besse

Research output: Contribution to journalArticlepeer-review


INTRODUCTION: This open-label, phase 1-2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).

METHODS: Patients with histologically or 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 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk 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 evaluate safety and tolerability and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1). The response-related results are based on centrally read data.

RESULTS: A total of 42 patients received therapy: cohort 1, n = 30; cohort 2, n = 12. Overall, 43% received two or more previous lines of therapy. All patients experienced one or more treatment-emergent adverse event (TEAE); 41 patients reported AEs considered related to the study drug by the investigator. The most frequent TEAE was pleural effusion (n = 20, 48%); most common grade greater than or equal to 3 was anemia (n = 9, 21%). Three grade 5 TEAEs considered related to the study drug were reported (cohort 1): pneumonitis (n = 2), acute kidney injury (n = 1). The objective response rate was 30% (12 of 40): cohort 1, 27.6% (8 of 29); cohort 2, 36.4% (4 of 11); all partial responses.

CONCLUSIONS: Despite encouraging antitumor activity in previously treated ES SCLC, combination therapy with Rova-T and nivolumab plus or minus ipilimumab was not well tolerated at the dose levels and administration schedules evaluated.

Original languageEnglish
Pages (from-to)1559-1569
Number of pages11
JournalJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Issue number9
Publication statusPublished - Sep 2021


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Benzodiazepinones
  • Humans
  • Immunoconjugates/therapeutic use
  • Ipilimumab/therapeutic use
  • Lung Neoplasms/drug therapy
  • Nivolumab/therapeutic use


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