Jyoti Malhotra1, Petros Nikolinakos2, Ticiana Leal3, Jonathan Lehman4, Daniel Morgensztern5, Jyoti D Patel6, John M Wrangle7, Giuseppe Curigliano8, Laurent Greillier9, Melissa L Johnson10, Neal Ready11, Gilles Robinet12, Satwant Lally13, David Maag14, Ricardo Valenzuela13, Vincent Blot14, Benjamin Besse15. 1. Rutgers Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ USA 08901. Electronic address: jm1940@cinj.rutgers.edu. 2. University Cancer & Blood Center, LLC, 3320 Old Jefferson Rd Bldg 700, Athens, GA USA 30607. 3. University of Wisconsin Carbone Cancer Center, 600 Highland Ave, Madison, WI USA 53705. 4. Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN USA 37232. 5. Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO USA 63110. 6. The University of Chicago Medical Center, 5841 S Maryland Ave, Chicago, IL USA 60637. 7. Medical University of South Carolina, 171 Ashley Ave, Charleston, SC USA 29425. 8. Istituto Europeo di Oncologia, IRCCS, and University of Milano, Via Ripamonti 435, 20141, Milano MI, Italy. 9. Assistance Publique - Hôpitaux de Marseille, Aix Marseille University, Hôpital de la Timone, 264 rue St Pierre, 13005 Marseille, France. 10. Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 250 25th Ave N, Nashville, TN USA 37203. 11. Duke University Medical Center, 10 Duke Medicine Cir Durham, NC USA 27710-1000. 12. CHU de Brest - Hôpital Morvan, 2 Avenue Foch, 29200 Brest, France. 13. AbbVie Stemcentrx, 450 E. Jamie Ct., South San Francisco, CA USA 94080. 14. AbbVie Inc., 1 North Waukegan Road North Chicago, IL USA 60064. 15. Gustave Roussy, 114, rue Édouard-Vaillant 94805 Villejuif Cedex - France; Paris-Saclay University, Espace Technologique Bat. Discovery - RD 128, 2e ét, 91190 Saint-Aubin, France.
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.
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.
Authors: Shane S Neibart; Daniella E Portal; Jyoti Malhotra; Salma K Jabbour; Jason A Roy; Brian L Strom Journal: Pharmacoepidemiol Drug Saf Date: 2021-08-23 Impact factor: 2.890