Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 2016 San Antonio Breast Cancer Symposium (SABCS)
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: epithelial cancers including triple-negative breast cancer, non-small cell lung cancer, small-cell lung cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This study is evaluating the safety and tolerability of IMMU-132 as a single agent administered in 3-week treatment cycles for up to 8 cycles, in previously treated patients with advanced epithelial cancer.The secondary objectives are to obtain initial data concerning pharmacokinetics, immunogenicity, and efficacy with this dosing regimen. This is planned as a multi-center study. In Phase II, up to 130 patients (assessable) in triple-negative breast cancer, up to 100 patients (assessable) in non-small cell and small-cell lung cancer and up to 50 patients (assessable) per other cancer types included in the protocol will be studied at the 10 mg/kg dose. (NCT01631552)
Latest
news: * On November 14, 2016, Immunomedics announced that three abstracts have been accepted for presentation at the 2016 San Antonio Breast Cancer Symposium (SABCS) to be held at the Henry B. Gonzalez Convention Center in San Antonio, TX, from December 6-10, 2016. Leading the presentations will be updates on the Phase 2 results of sacituzumab govitecan (IMMU-132) in patients with metastatic triple-negative breast cancer (TNBC). Based on earlier results from this single-arm study, the FDA has designated sacituzumab govitecan a Breakthrough Therapy for patients with TNBC who have received two or more prior treatments for their metastatic disease. The updated results to be presented at SABCS will form part of a biologics license application (BLA) the Company plans to submit to the FDA in mid- 2017 for accelerated approval in * On June 28, 2016, Immunomedics related its updated clinical development plan for sacituzumab govitecan in * On December 10, 2015, Immunomedics announced updated results from a Phase 2 clinical study of sacituzumab govitecan, its lead investigational antibody-drug conjugate (ADC), in patients with metastatic triple-negative breast cancer (mTNBC) who had received a median of 5 (range, 2 -- 12) prior lines of therapy. Despite this late-stage setting, the ADC, as a single agent, produced an interim ORR of 31% by RECIST 1.1 in 58 evaluable patients, with 78% of these responding patients confirmed with a follow-up computed tomography scan, including 2 patients with a complete response. Among the 60 intent-to-treat patients, the interim median PFS was 6.0 months, with 58% of these patients having experienced a PFS event. Importantly, there is a significant positive correlation between PFS and maximal tumor shrinkage relative to baseline (R=0.62, P<0.001) for the 31 patients whose cancer had progressed after reporting stable disease, partial or complete response as their best response. Median overall survival data were too early to report, with 83% of patients still alive. Sacituzumab govitecan has an acceptable interim safety profile in the 60 mTNBC patients reported at the Symposium. The major toxicity was Grade 3 or 4 neutropenia in 15% of patients. Severe diarrhea, commonly reported with irinotecan, was rare with only 5% Grade 3/4 incidents. Moreover, repeated doses can be given over months without evoking interfering anti-sacituzumab govitecan antibodies from patients' own immune system. Immunomedics has filed a multicenter, international, randomized, open-label Phase 3 study of approximately 328 patients with mTNBC who are refractory or relapsing after at least 2 prior chemotherapies that included a taxane for their metastatic disease. * On October 19, 2015, Immunomedics announced that sacituzumab govitecan produced durable responses that exceeded one year in some patients with metastatic triple-negative breast (TNBC), small-cell (SCLC) and non-small-cell lung (NSCLC) cancers. In other patients with less than 1 year of response duration, their responses are continuing.
TNBC, based on a recent Breakthrough Therapy Designation (BTD) and a follow-on meeting with the FDA.
In the fall of this year, the Company plans to complete enrolling additional patients with relapsed/refractory metastatic TNBC who have received at least two prior therapies, including taxane, for metastatic disease into the ongoing single-arm Phase 2 study. Results from this Phase 2 study are expected to support the clinical requirements for pursuing Accelerated Approval. All patients receive repeated cycles of sacituzumab govitecan at the dose of 10 mg/kg on days 1 and 8 of a twenty-one day cycle. Treatment responses, including overall response rate and duration of response, are assessed with computed tomography (CT) in accordance with RECIST 1.1, and
confirmed by an independent centralized and blinded group of radiology experts.
The Company is working with the FDA on these plans for completing the ongoing Phase 2 trial and for submitting an Accelerated Approval registration application, based on interactions with the agency. Furthermore, initial discussion has also occurred with the European Medicine Agency (EMA), which has provided the Company with advice on its planned Phase 3 trial.
“This enrollment timeline will allow us to have at least six months of patient follow-up to obtain a confirmed response rate and a mature duration of response, which will be part of an Accelerated Approval application estimated to be submitted to the regulatory agency by the middle of calendar year 2017,” noted William A. Wegener, M.D., Ph.D., Chief Medical Officer of Immunomedics. “It will also allow us to have our Phase 3 trial, which we have reached agreement with FDA on a Special Protocol Assessment (SPA), well underway, as required by the FDA for Accelerated Approval,” he further remarked.
Dr. David M. Goldenberg, Chairman, Chief Scientific Officer and Chief Patent Officer, presented the results at the 2015 World ADC San Diego conference. The presentation on TNBC focused on those patients who relapsed after 2 or more prior lines of therapy that included taxane. At the time of this analysis, 56 enrolled patients had received sacituzumab govitecan at the optimal dose of 10 mg/kg given on days 1 and 8 of a 3-week cycle, and in some patients the therapy continued for many months. The median number of prior lines of therapy for the patients enrolled with metastatic TNBC was 5 (range, 2 – 12). Treatment response, assessed by computed tomography (CT) according to the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1), was available for 52 patients. The objective response rate was 29% (15/52), with 2 confirmed complete responses. The interim
median progression-free survival (PFS), a measure of time patients are living without their cancer progressing, was 7.0 months, which appears to be longer than the best PFS results in this patient setting achieved by currently-used agents. Forty-six percent of these TNBC patients had experienced a PFS event. Overall survival (OS) data were too early to report because 86% of patients are still alive.
For metastatic lung cancers, a total of 33 patients with NSCLC, having received a median of 3 (range, 1 – 7) prior therapies, were enrolled to receive sacituzumab govitecan at the 8.0 mg/kg or 10 mg/kg dose level. Among the 29 patients that were assessable, an objective response (partial response) rate of 28% (8/29) was observed, including patients with both squamous cell and adenocarcinoma NSCLC types. For the 25 patients at the 10 mg/kg dose, the interim median PFS was 3.8 months, with 48% of patients in this dose group having experienced a PFS event.
In SCLC, of the 27 patients, with a median of 3 prior therapies (range 1 – 5), enrolled at the doses of 8.0 mg/kg and 10 mg/kg, 25 were assessable for response. Six patients achieved a partial response (objective response rate = 24%). Interim median PFS for the 12 patients at the 10 mg/kg dose level was 3.6 months and 83% of patients had experienced a PFS event. Since 96% of NSCLC patients and 100% of SCLC patients were still alive at the time of analysis, OS data at the optimal dose of 10 mg/kg are too early to report.
Sacituzumab govitecan continues to demonstrate a highly tolerable safety profile. Among the 261 patients enrolled to-date, only 8 patients had reported adverse events that temporarily interrupted the infusion. In the 118 patients receiving the ADC at the dose of 10 mg/kg, the major toxicity reported was Grades 3 or 4 neutropenia in 20% of patients.
