1748PPhase I open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer

• Published in: Annals of oncology Vol. 30; no. Supplement_5
• Main Authors: Calvo, E, Spira, A, Prenen, H, Ohe, Y, Rottey, S, Gazzah, A, Millward, M, Moreno, V, Italiano, A, Alanko, T, Yoh, K, Cassier, P A, Seto, T, Afar, D, Englert, S, Komarnitsky, P, Lambert, S, Parikh, A, Vosganian, G, Gao, B
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz264.012

Abstract Background ABBV-181 is a humanized anti-programmed cell death 1 (PD-1) monoclonal antibody with activity in solid tumors. ROVA-T is an immunoglobulin G1 antibody-drug conjugate targeting cell surface delta-like protein 3 (DLL3) incorporating the pyrrolobenzodiazepine-based DNA cross-linking agent SC-DR002, for which safety and activity in small cell lung cancer (SCLC) has been reported. This report summarizes data from SCLC patients (pts) treated with ABBV-181 and ROVA-T in study NCT03000257. Methods Pts with previously treated SCLC received 2 doses of ROVA-T 0.3 mg/kg intravenously (IV) every 6 weeks (Q6W) and ABBV-181 375 mg IV Q3W to progression. Response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune RECIST. Serial pharmacokinetic (PK) and pharmacodynamic (PD) samples were collected. Results As of 5 April 2019, 31 pts were dosed. Table: 1748Pn (%)Median days on ABBV-181 treatment, range58.5, 10–358.0Doses of ROVA-T1: 15 (48.0); 2: 16 (52.0)Grade (G) ≥1 adverse events (AEs)31 (100.0)G ≥ 3 AEs25 (80.6)ABBV-181-related G ≥ 3 AEs9 (29.0)ROVA-T-related G ≥ 3 AEs12 (38.7)AEs resulting in discontinuation of ABBV-181a,b / ROVA-Tc,d6 (19.4) / 3 (9.7)G5 AEse2 (6.5)aFour (12.9%) ABBV-181-related, 1 each of immune-related hepatitis, colitis, general physical health deterioration, and peripheral sensory neuropathy.bOne (3.2%) ROVA-T-related, of peripheral sensory neuropathy.cOne (3.2%) ABBV-181-related, of general physical health deterioration.dOne (3.2%) ROVA-T-related, of thrombocytopenia.eUnrelated to either ABBV-181 or ROVA-T (1 [3.2%] malignant neoplasm progression and 1 [3.2%] depressed level of consciousness) The most frequent AEs of any grade included: fatigue, 12 pts (38.7%), decreased appetite and nausea, 9 pts each (29.0%). ABBV-181 and ROVA-T PK were not impacted by the combination regimen when compared with dose-normalized ABBV-181 PK or ROVA-T PK alone. PD-1 saturation on circulating CD4+ T cells, and increased Ki67+ CD8+ T cells and serum chemokine C-X-C ligand 9 (CXCL9)/CXCL10 were observed, consistent with previous ABBV-181 reports. In pts with ≥1 post-baseline assessment, investigator-assessed best overall response and objective response rates were 9/29 and 4/29 (including 1 complete response in each). Conclusions The combination of ROVA-T and ABBV-181 has an adequate safety profile and preliminary efficacy, with no impact on the PK/PD characteristics of either agent. Additional follow-up is required to characterize safety, efficacy, and associations with PD-L1/DLL3 expression for this combination. Clinical trial identification NCT03000257. Editorial acknowledgement Oana Draghiciu, PhD, CMPP, from Aptitude Health, The Hague, The Netherlands; funded by AbbVie. Legal entity responsible for the study AbbVie Inc. Funding AbbVie Inc. Disclosure E. Calvo: Honoraria (self), (Or consultation fees): Astellas; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Novartis; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Nanobiotix; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Pfizer; Honoraria (self), (Or consultation fees): Janssen-Cilag; Honoraria (self), (Or consultation fees): GLG Pharma; Honoraria (self), (Or consultation fees): PsiOxus Therapeutics; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Merck; Honoraria (self), (Or consultation fees): Medscape; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Bristol-Myers Squibb; Honoraria (self), (Or consultation fees): Gilead Sciences; Honoraria (self), (Or consultation fees): Seattle Genetics; Honoraria (self), (Or consultation fees): Pierre Fabre; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): Boehringer Ingelheim; Honoraria (self), (Or consultation fees): Cerulean Pharma; Honoraria (self), (Or consultation fees): EUSA Pharma; Honoraria (self), (Or consultation fees): Gehrmann Consulting; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution), (Or consultation fees): AstraZenenca; Honoraria (self), (Or consultation fees): Roche; Honoraria (self), (Or consultation fees): Guidepoint; Honoraria (self), (Or consultation fees): Servier; Honoraria (self), (Or consultation fees): Celgene; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): AbbVie; Honoraria (self), Research grant / Funding (institution), (Or consultation fees): amcure; Honoraria (self), (Or consultation fees): OncoDNA; Honoraria (self), (Or consultation fees): Alkermes; Leadership role, Full / Part-time employment: director clinical research, START Madrid (Program of Early Phase Clinical Drug Development in Oncology); Leadership role, Full / Part-time employment: director clinical research, HM Hospitals Group, Madrid; Leadership role: founder and president, non-for-profit Foundation INTHEOS (Investigational Therapeutics in Oncological Sciences); Leadership role: co-director, Methods in Clinical Cancer Research (MCCR) Workshop, Zeist, Netherlands (joint ECCO-AACR-EORTC-ESMO Workshop on MCCR); Shareholder / Stockholder / Stock options, Full / Part-time employment, (Or ownership): START; Shareholder / Stockholder / Stock options, (Or ownership): Oncoart Associated; Shareholder / Stockholder / Stock options, (Or ownership): International Cancer Consultants; Research grant / Funding (self): Novartis; Research grant / Funding (self), Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): ACEO; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): CytomX Therapeutics; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): H3 Biomedicine; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Kura; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Menarini; Research grant / Funding (institution): Merus; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Principia; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Innovio; Research grant / Funding (institution): MSD; Research grant / Funding (institution), Non-remunerated activity/ies: PsiOxus; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Daiichi; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): ORCA; Research grant / Funding (institution): Boston Therapeutics; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): Debiopharm; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Millenium; Research grant / Funding (institution): Synthon; Research grant / Funding (institution): Spectrum; Research grant / Funding (institution): Rigontec; Non-remunerated activity/ies: Memberships for SEOM, EORTC, ESMO, and ASCO. A. Spira: Honoraria (self), Research grant / Funding (institution): CytomX Therapeutics; Honoraria (self): AstraZeneca/MedImmune; Honoraria (self): Merck; Advisory / Consultancy: Array BioPharma; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): NewLink Genetics; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ignyta; Research grant / Funding (self), Research grant / Funding (institution): LAM Therapeutics; Research grant / Funding (institution): TrovaGene; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Astex Pharmaceuticals; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Arch. H. Prenen: Honoraria (self): Roche; Honoraria (self): Bayer; Honoraria (self): Amgen; Honoraria (self): Ipsen; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Sanofi; Honoraria (self): Merck; Honoraria (self): Vfor Pharma; Honoraria (self): Lilly. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): ONO; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Advisory / Consultancy: Celltrion; Advisory / Consultancy: Amgen; Research grant / Fun