Therapy of advanced metastatic lung cancer with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase I/II clinical experience.

2504 Background: Sacituzumab govitecan (IMMU-132) is a new ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, camptothecin (irinotecan), conjugated to an anti-Trop-2 antibody. In vitro and in vivopreclinical data suggest that IMMU-132 is a unique ADC, being most efficacious at a high drug-antibody ratio (DAR) of 7.6, and capable of delivering up to 136-fold more SN-38 than its parental drug, irinotecan, in a human cancer xenograft. Trop-2 is widely expressed in most epithelial cancers, including non-small and small cell lung cancers (NSCLC and SCLC). Therefore, the safety and efficacy of this new ADC is being examined in advanced metastatic lung cancers. Methods: A phase I/II clinical trial (ClinicalTrials.gov, NCT01631552) is ongoing in subsets of previously-treated patients with metastatic lung cancer, administering IMMU-132 on days 1 and 8 of 21-day treatment cycles. Treatment is continued based on tolerance or until progression, with safety and response assessments made every week and at 8-12 weeks, respectively. Dose reductions and delays allowed most patients to continue treatment until progression. Results: Thirty-four lung cancer (15 NSCLC and 19 SCLC) patients with a median of 3 (range, 1-7) prior therapies were given IMMU-132 doses at 8 mg/kg (N = 22), 10 mg/kg (N = 10), 12 mg/kg (N = 2). Tumor responses, including squamous and adenocarcinoma NSCLC types having PR, are summarized in the table below. Neutropenia was the only Grade 3/4 toxicity (G3, 15%; G4, 3%). Other drug-related G3 toxicities included diarrhea (9%), anemia (6%), leucopenia (3%), lymphopenia (3%), pneumonia (3%), vomiting (3%), dizziness (3%). No differences were found between 8 and 10 mg/kg dosing. No pt developed antibodies (ELISA) to the conjugate. Conclusions: Repeated cycles of IMMU-132 monotherapy are well tolerated. Objective responses in previously treated metastatic lung cancer encourage further study of IMMU-132 in these cancers. Clinical trial information: NCT01631552. Tumor type PR Disease stabilization (PR+SD) Clinical benefit (PR+ SD) > 6 mo Median TPP (Mo) NSCLC (N = 15) 27% 73% 42% 3.3+ SCLC (N = 19) 26% 53% 29% 2.8+