Date: 2016-06-06
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Immunomedics (USA - NJ)
Product: sacituzumab govitecan - IMMU-132
Action
mechanism: antibody drug conjugate/ADC. Sacituzumab govitecan, or IMMU-132, is a first-in-class ADC developed by Immunomedics by conjugating the moderately-toxic drug, SN-38 (active metabolite of irinotecan), site-specifically and at a high ratio of drug to antibody, to a humanized antibody that targets the TROP-2 receptor expressed by many solid cancers. SN-38 is the active metabolite of irinotecan (Camptosar), which is used to treat certain solid cancers as a part of combination therapies, so its pharmacology and properties are well-known. IMMU-132 targets the TROP-2 antigen which is expressed on a variety of cancers. The ADC has received Fast Track designation from the FDA for the treatment of patients with triple-negative breast cancer, small-cell and non-small-cell lung cancers, and has also been designated an orphan drug for the treatment of patients with small-cell lung or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the European Union.
Disease: metastatic non-small-cell lung cancer (NSCLC),
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On June 6, 2016, Immunomedics announced that sacituzumab govitecan (IMMU-132), its lead investigational antibody-drug conjugate (ADC), shrank tumors by 30% or more initially in 26% (12/46) of evaluable patients with metastatic non-small-cell lung cancer (NSCLC), with a later confirmed overall objective response rate (ORR) of 13%, in accordance with RECIST 1.1 criteria. For the patients with confirmed responses, the duration of response (DOR) was 9 months. Interim median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95% confidence interval [CI]; 3.4, 6.9) and 10.5 months (95% CI; 5.8, 10.5), respectively. Significant tumor shrinkage and disease stabilization was observed in both adenocarcinoma and squamous cell carcinomas, the two major subtypes of NSCLC, and in patients who had failed previous antiPD-1/PD-L1 therapy. Sacituzumab govitecan directs SN-38, the active moiety of irinotecan, preferentially towards tumor cells by using an antibody targeted against Trop-2 – a commonly expressed surface marker on epithelial cancers. At the recommended dose of 10 mg/kg given intravenously on days 1 and 8 of 21-day repeated cycles, sacituzumab govitecan had a manageable safety profile in the absence of mandated growth factor, anti-nausea and anti-diarrheal prophylaxis, with 29% Grades 3 and 4 neutropenia as the major toxicity and minimal (7%) Grade 3 and 4 diarrhea, which, historically, has been a major side-effect with irinotecan. “Any interpretation of either the efficacy or safety data on IMMU-132 in lung cancer patients from this trial has to take into account that the patients had a median of 3 prior therapies. In such a heavily-pretreated population and because prophylactic supportive care was not part of the protocol from Cycle 1, the safety data on this drug is really quite striking. Some people need dose reductions, but in general it’s a pretty easy drug to give. While the severe neutropenia rate is comparable, the severe diarrhea rate is less than a third of that seen with irinotecan in previous studies in lung cancer conducted in the pure second line setting,” 1 commented D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, who presented these results at the Clinical Science Symposium on Raising the Bar for Targeted Therapies for Lung Cancers of the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO). “While the confirmed response rate is modest at 13%, the duration of these responses to date is impressive, over double that seen with irinotecan alone in the same historical lung cancer studies.” Dr. Camidge also updated the results from 12 patients who had prior anti-PD-1/PD-L1 therapies. Eight of these patients showed either stable disease or partial responses with sacituzumab govitecan, including one patient with squamous cancer achieving a partial response, awaiting confirmation. “The potential for non-overlapping cross-resistance with anti-PD-1/PD-L1 therapy is intriguing and suggests several paths forward for this drug in the era of routine immunotherapy,” remarked Dr. Camidge.
