PMID- 33340277 OWN - NLM STAT- MEDLINE DCOM- 20211208 LR - 20211214 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 14 IP - 2 DP - 2021 Mar TI - Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small-Cell Lung Cancer. PG - 664-670 LID - 10.1111/cts.12928 [doi] AB - Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate that targets delta-like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova-T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova-T in patients with previously treated extensive-stage SCLC. Patients underwent ECG monitoring for 2 weeks after each of 2 i.v. infusions of 0.3 mg/kg Rova-T over 30 minutes, administered 6 weeks apart. Forty-six patients received at least one dose of Rova-T. At the geometric mean Rova-T maximum serum concentration of 7,940 ng/mL, ECG monitoring showed no significant changes in the Fridericia-corrected QT (QTcF) interval; the upper limit of the 2-sided 90% confidence interval did not exceed 10 msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova-T administration. All patients experienced a treatment-emergent AE (TEAE); 78% had a grade >/= 3 TEAE, 59% had a serious TEAE, and 41% had a cardiac-related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova-T at 0.3 mg/kg i.v. administered every 6 weeks, a QTcF effect of clinical concern can be excluded. CI - (c) 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. FAU - Goldman, Jonathan W AU - Goldman JW AD - David Geffen School of Medicine at UCLA, Los Angeles, California, USA. FAU - Barve, Minal AU - Barve M AD - Mary Crowley Cancer Research Center, Dallas, Texas, USA. FAU - Patel, Jyoti D AU - Patel JD AD - Lurie Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Wozniak, Antoinette AU - Wozniak A AD - Hillman Cancer Center at University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. FAU - Dowlati, Afshin AU - Dowlati A AD - University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA. FAU - Starodub, Alexander AU - Starodub A AD - Riverside Peninsula Cancer Institute, Newport News, Virginia, USA. FAU - Owonikoko, Taofeek K AU - Owonikoko TK AD - Winship Cancer Institute of Emory University, Atlanta, Georgia, USA. FAU - Edenfield, William AU - Edenfield W AD - Prisma Health Cancer Institute, Greenville, South Carolina, USA. FAU - Laurie, Scott A AU - Laurie SA AD - Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. FAU - Da Costa, Daniel AU - Da Costa D AD - AbbVie, Inc., Illinois, North Chicago, USA. FAU - Lally, Satwant AU - Lally S AD - AbbVie, Inc., Illinois, North Chicago, USA. FAU - Koch, Martina AU - Koch M AD - AbbVie, Inc., Illinois, North Chicago, USA. FAU - Kosloski, Matthew P AU - Kosloski MP AD - AbbVie, Inc., Illinois, North Chicago, USA. FAU - Hoffman, David AU - Hoffman D AD - AbbVie, Inc., Illinois, North Chicago, USA. FAU - Dy, Grace K AU - Dy GK AD - Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20201219 PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Benzodiazepinones) RN - 0 (Immunoconjugates) RN - 0 (rovalpituzumab tesirine) SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects MH - Antineoplastic Agents/administration & dosage/*adverse effects MH - Benzodiazepinones/administration & dosage/*adverse effects MH - Cardiotoxicity/diagnosis/etiology MH - Electrocardiography/drug effects MH - Female MH - Heart Rate/drug effects MH - Humans MH - Immunoconjugates/administration & dosage/*adverse effects MH - Long QT Syndrome/chemically induced/*diagnosis MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Small Cell Lung Carcinoma/*drug therapy PMC - PMC7993269 COIS- J.G. received research funding from Stemcentrx and AbbVie. J.P. had a consultancy/advisory role for AbbVie, AstraZeneca, Genentech, and Takeda and received research funding to institution from Bristol Myers Squibb. A.W. had a consultancy/advisory role for Boehringer Ingelheim, AstraZeneca, Premier, Inc., Lilly Oncology, Karyopharm, and Epizyme, served on a data safety monitoring board for Odonate Therapeutics, BeyondSpring Pharmaceuticals, and HUYA Bioscience International, and received research funding from Boehringer Ingelheim. A.D. had a consultancy/advisory role for Takeda, AbbVie, Seagen, AstraZeneca, and Bristol Myers Squibb and received research funding from Loxo, Bayer, Incuron, Takeda, Regeneron, Tesaro, Amgen, Seagen, Symphogen, AbbVie, and Ipsen. A.S. had a consultancy/advisory role with Sandoz and Bayer, and received honorarium from Bristol Myers Squibb. T.O. had a consultancy/advisory role for AbbVie. W.E. had a consultancy/advisory role for Chimerix. S.L. received research funding to institution from AbbVie. D.D.C., S.L., M.K., and D.H. are employed by AbbVie and may hold stock or other options with AbbVie. M.K. is employed by Regeneron and may hold stock or other options with Regeneron and was a former employee of AbbVie. G.D. had a consultancy/advisory role for and honorarium from AbbVie. All other authors declared no competing interests for this work. EDAT- 2020/12/20 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/03/01 CRDT- 2020/12/19 08:36 PHST- 2020/08/11 00:00 [received] PHST- 2020/09/10 00:00 [accepted] PHST- 2020/12/20 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2020/12/19 08:36 [entrez] PHST- 2021/03/01 00:00 [pmc-release] AID - CTS12928 [pii] AID - 10.1111/cts.12928 [doi] PST - ppublish SO - Clin Transl Sci. 2021 Mar;14(2):664-670. doi: 10.1111/cts.12928. Epub 2020 Dec 19.