SC-002 in patients with relapsed or refractory small cell lung cancer and large cell neuroendocrine carcinoma: Phase 1 study

Abstract

Objectives: This phase 1 study investigated safety/tolerability, pharmacokinetics, and preliminary efficacy of SC-002, a delta-like ligand 3-directed antibody-drug conjugate, in advanced small cell lung cancer and large cell neuroendocrine carcinoma.

Materials and methods: Eligible patients received SC-002 at 1 of 7 dose levels during the dose-escalation portion of the study.

Results: Thirty-five enrolled patients received ≥1 dose of SC-002. Twenty-three (66%) patients experienced serious adverse events (AEs), 37% considered related to SC-002. Grade 3/4 AEs occurred in 21 (60%) and 2 (6%) patients; the most common were effusion and hypoalbuminemia. One grade 5 AE occurred in 1 patient. Five (14%) patients achieved a partial response and no patients achieved a complete response.

Conclusion: SC-002 treatment was associated with systemic toxicity and limited efficacy.

Trial registration: ClinicalTrials.gov NCT02500914.

Keywords: Antibody-drug conjugate; Delta-like ligand 3; Large cell neuroendocrine carcinoma; Pyrrolobenzodiazepine; SC-002; Small cell lung cancer.

Conflict of interest statement

Declaration of Competing Interest Daniel Morgensztern: Consultant fees: AbbVie, Bristol-Myers Squibb, PharmaMar, Boehringer Ingelheim, Takeda, Gilead. Melissa Johnson: Research funding to institution: AbbVie, Acerta, Adaptimmune, Apexigen, Array BioPharma, AstraZeneca, Atreca, BeiGene, Birdie, Boehringer Ingelheim, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dynavax, Lilly, EMD Serono, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati Therapeutics, Neovia Oncology, Novartis, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Sanofi, Shattuck Labs, Stemcentrx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, Amgen; consulting/advisory role (spouse): contract lobbyist for Astellas, contract lobbyist for Otsuka Pharmaceuticals; consulting/advisory role (self) – all to institution: AbbVie, Achilles Therapeutics, AstraZeneca, Atreca, Boehringer Ingelheim, Calithera Biosciences, Genentech, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Incyte, Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics, Novartis, Pfizer, Ribon Therapeutics, Sanofi, Association of Community Cancer Centers; food/beverage/travel expenses: AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, EMD Serono, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Incyte, Merck, Pfizer, Sysmex Inostics, Vapotherm, Janssen, Lilly, Novartis, Sanofi. Charles M. Rudin: Consultant for: AbbVie, Amgen, Ascentage, AstraZeneca, Celgene, Daiichi Sankyo, Genentech/Roche, Ipsen, Loxo, PharmaMar, and Vivotek. Scientific advisory boards of Bridge Medicines and Harpoon Therapeutics. Michael Rossi, Mirella Lazarov, Daniel Brickman, Abraham Fong: AbbVie employees and may own stock.

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