Date: 2016-05-02
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at PEGS Boston 2016
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. Sacituzumab govitecan has also been granted Breakthrough Therapy Designation from the FDA for the treatment of patients with triple-negative breast cancer (TNBC) who have failed prior therapies for metastatic disease.
Disease: advanced, metastatic solid cancers
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 29, 2016, Immunomedics announced that objective durable responses have been achieved with sacituzumab govitecan in a number of patients with advanced, metastatic solid cancers, after failing multiple prior therapies, some including checkpoint inhibitors (CPIs). Treatment responses, assessed by computed tomography (CT) according to the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1), are summarized in the table below. These results include objective response rate (ORR), progression-free survival (PFS), a measure of time patients are living without their cancer progressing, and overall survival (OS) in patients with metastatic TNBC, non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC) and urothelial cancer (UC). Most of the TNBC and all of the UC patients’ objective responses were confirmed by subsequent CT studies, while follow-up in many patients with NSCLC and SCLC is ongoing. (a) Numbers in parenthesis represent median number and the range of prior therapies. Results from 8 patients with metastatic NSCLC who had failed prior CPI therapies have also been presented. Seven of these patients had recently enrolled into the Phase 2 study with sacituzumab govitecan. Despite the short duration of their treatment with the ADC, one patient with squamous cell carcinoma has a partial response (PR) while the remaining patients reported stable disease (SD) as their best response. Three of those SD responders have tumor shrinkage of 13 to 28%. These patients are continuing their therapy with sacituzumab govitecan. (a) N=Nivolumab, A=Atezolizumab. In his presentation, Dr. Goldenberg also highlighted 14 patients who had received extensive sacituzumab govitecan treatment of 56 to 95 weeks, with 11 of these patients continuing with their treatment as of March 23, 2016. Ten patients with TNBC, NSCLC or SCLC are partial responders. All but one of the PRs have been confirmed. Despite repeated dosing, no interfering anti-sacituzumab govitecan antibodies were detected in these or any other patients to-date. Sacituzumab govitecan is well tolerated by all patients. In the 128 patients receiving the ADC at the dose of 10 mg/kg, interim Grades 3 or 4 adverse events with greater than 2% incidence include neutropenia in 34% of patients, followed by diarrhea (11%) and febrile neutropenia (9%). The protocol does not require pretreatment of patients prior to receiving sacituzumab govitecan.Cancer Type # of Assessable Patients(a) % ORR
(% Confirmed)Median PFS(c)
(% Maturity)Median OS
(% Maturity)TNBC 58 (5, 2 – 12) 34%(b) (75%) 5.7 months (62%) Not Reached NSCLC 32 (3, 1 – 7) 31% (30%) 3.9 months (68%) Not Reached SCLC 26 (2.5, 1 – 5) 23% (50%) 2.1 months (82%) 8.1 months (54%) UC 14 (2, 1 – 5) 50% (100%) 6.9 months (47%) 11.4 months(d)(16%)
(b) Includes 2 patients with a complete response.
(c) Based on number of intent-to-treat patients of 60, 34, 28 and 14 for TNBC, NSCLC, SCLC and UC, respectively.
(d) Mean OS result reported.NSCLC Patient # # of Prior Tx CPI(a) # line CPI Response to CPI CPI Tx Duration (mos.) IMMU-132 Doses IMMU-132 Best Response Target Lesion Best % Change Histology(b) PFS (mos.) 1 2 N 2 Yes 8 9 SD 0 SQ 1.2+ 2 6 N 2 N/A 1 5 SDc 7 AC 3.7+ 3 1 A 1 Yes 23 4 SD -13 AC 1.8+ 4 6 A 4 No 3 10 SDc -23 AC 3.1+ 5 2 N 2 No 9 6 SDc -28 AC 2.7+ 6 3 A 3 No 2 6 SD 1 AC 1.6+ 7 3 N 3 No 6 5 PR -50 SQ 2.0+ 8 3 N 3 No 5 6 SD 10 AC 1.9+
(b) SQ=squamous cell carcinoma, AC=adenocarcinoma.
