Sacituzumab govitecan

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Immunomedics (IMMU) Announces Significant Data from Sacituzumab Govitecan in Tumor Shrinkage


Immunomedics (NASDAQ: IMMU) announced that, in a mid-stage clinical study, a multitude of patients with late stage solid cancers showed significant and durable tumor shrinkage after receiving treatments with sacituzumab govitecan, the Company's lead antibody-directed chemotherapeutic agent in development. These include patients with metastatic triple-negative breast cancer whose cancers after treatment were no longer detected by computed tomography, a test commonly used to find and locate tumors, and to measure a patient's treatment response.

"All of these patients had failed many prior therapies for their cancers and were running out of options before being treated with sacituzumab govitecan," stated Dr. Alexander N. Starodub of the Indiana Health Center for Cancer Care, Goshen, Indiana, one of the Principal Investigators. "In this respect, we are very encouraged with the responses we are reporting at this year's Annual Meeting of the American Association for Cancer Research, especially in light of the fact that this novel agent is given to patients as a monotherapy, and not part of a drug cocktail. I believe sacituzumab govitecan has the potential to become a viable alternative for treating patients with advanced, metastatic solid cancers if these results are confirmed in a late-stage clinical trial," added Dr. Starodub.

At the time of analysis, a total of 184 patients with many different advanced, metastatic cancers were enrolled into the study. Dr. Starodub's oral presentation focused on interim responses from 130 patients having these four major solid cancer types: breast, lung, esophageal, and colorectal.

For patients with triple-negative breast cancer, 26% showed objective response to sacituzumab govitecan, with 2 having a complete disappearance of their tumors, or complete response, and 10 showing a 30% or better tumor reduction, which qualified them as partial responders in accordance with the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Including patients with responses between less than 30% tumor shrinkage and less than 20% tumor increase, which are considered stable disease, the disease control rate was 74%. At present, 21 of these patients are continuing therapy.
Cancer Types (N*)        Objective Response**        Disease Control
Triple-Negative Breast (46)        (2+10) (26%)        34 (74%)
Non-Small Cell Lung (19)        6 (32%)        14 (74%)
Small Cell Lung (20)        6 (30%)        11 (55%)
Esophageal (16)        2 (13%)        9 (56%)

* N represents the number of patients that are evaluable at this time for treatment response.

** Except with triple-negative breast cancer (2 patients with complete response), all objective responses are partial responses.

In lung cancer, the objective response rates were 32% and 30% for non-small-cell and small-cell lung cancers, respectively, and disease control rates were 74% and 55%, respectively. "These results compare very favorably to all other agents used in this disease and setting," commented Dr. Starodub. For the 18 patients with advanced cancer of the esophagus enrolled into the study, 16 were assessable for response, having an objective response rate of 13% and a disease control rate of 44%.

Also reported were results on 29 patients with colorectal cancer in early assessments of survival. The median length of time living without the disease getting worse from the beginning of their sacituzumab govitecan treatments was 3.9 months. The median length of survival from the start of treatment was 18.0 months. "These are very encouraging preliminary results for patients who had a median of 4 prior therapies for metastatic colorectal cancer, some as many as 8," remarked Dr. Starodub.

Commenting on these encouraging results, Ms. Cynthia L. Sullivan, President and Chief Executive Officer stated, "We are in discussion with FDA to formulate a registration pathway for sacituzumab govitecan to advance the agent to a Phase 3 registration trial." "We are completing the enrollment of additional patients with triple-negative breast cancer, non-small and small-cell lung cancers. Our ultimate goal is to develop the full potential of this important and valuable asset for the benefits of cancer patients by advancing it with a corporate partner," Ms. Sullivan concluded.

Sacituzumab govitecan was created by the Company for the therapy of solid cancers by selectively delivering the active anticancer drug, SN-38, to a target called TROP-2 that is produced in high amounts by cancer cells relative to normal tissues. These cancers include breast, lung, esophageal, stomach, colon, rectal, pancreatic, prostate, ovarian, urinary bladder, and uterine cancers.

SN-38 is formed in the body from irinotecan, a drug used in various combinations to treat patients with colorectal and other cancers. However, the process of converting irinotecan to the active SN-38 is inefficient, which lowers the efficacy of irinotecan. By attaching active SN-38 directly to a tumor-targeting antibody, as much as 136-times more SN-38 can be delivered directly to the tumor than when irinotecan is administered, without increasing the toxicity to the body at the same time.

Sacituzumab govitecan is well tolerated by patients. At the optimal doses of 8 and 10 mg/kg, only 7% of patients required having dosing delayed due to adverse reactions, while dose reductions were experienced in only 15-16% of patients. Grades 3 and 4 adverse events occurring in more than 5% of patients include fatigue (5%), neutropenia (24%), and anemia (6%). Irinotecan shows an increased incidence of severe diarrhea (38%), neutropenia (31%), and neutropenic fever (8%). Further, despite repeated injections, no patient produced any antibody against sacituzumab govitecan.

In addition to Dr. Starodub, other clinical investigators participated in this multicenter trial are Drs. Allyson J. Ocean, Linda T. Vahdat, Scott T. Tagawa, and Manish A. Shah, Weill Cornell Medical College, New York, NY; Dr. Aditya Bardia, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; Drs. Michael J. Guarino and Gregory A. Masters, Helen F. Graham Cancer Center & Research Institute, Newark, DE; Drs. Wells A. Messersmith and Jennifer S. Diamond, University of Colorado Cancer Center, Aurora, CO; Drs. Jordan Berlin and Ingrid A. Mayer, Vanderbilt-Ingra Cancer Center, Nashville, TN; Dr. Vincent J. Picozzi, Virginia Mason Cancer Center, Seattle, WA; and Drs. Sajeve S. Thomas and Rebecca Moroose, UF Health Cancer Center-Orlando Health, Orlando, FL.

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Immunomedics (IMMU) Reports Data on Sacituzumab Govitecan in Lung Cancer


Immunomedics, Inc., (Nasdaq: IMMU) today announced that 33% of patients with small cell lung cancer (SCLC) and 31% with non-small cell lung cancer (NSCLC) had their tumor reduced in size by 30% or more, after being treated with sacituzumab govitecan, the Company's lead investigational antibody-drug conjugate (ADC). Including patients that reported stable disease as their best response, the ADC controls the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed.

Dr. Francois Wilhelm, Chief Medical Officer, presented the updated results at the 15th Annual Targeted Therapies of Lung Cancer Meeting, an invitation-only meeting sponsored by The International Association for the Study of Lung Cancer (IASLC).

Sacituzumab govitecan is a next generation ADC designed for targeted therapy of solid cancers. The agent was created by site-specifically conjugating a TROP-2-targeting antibody with a high ratio of a moderately toxic drug, SN-38, using a pH sensitive linker. TROP-2 is a receptor found on many human cancer cells, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. In an animal model of human pancreatic cancer, the ADC delivered up to 135-times the amount of SN-38 to the tumor than when irinotecan, the parent drug of SN-38, was given.

A total of 44 heavily-pretreated patients with relapsed or refractory lung cancer have been enrolled into this multicenter study. At the time of analysis, 16 patients with SCLC and 18 with NSCLC were evaluated by computed tomography for response and time-to-progression (TTP). Despite the late-stage setting, TTP for most patients was longer with sacituzumab govitecan than the duration of their previous lung cancer therapy.

NSCLC is the most common type of lung cancer, accounting for more than 85% of new diagnoses. There are three main subtypes of NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Patients with advanced-stage NSCLC are usually treated with chemotherapy, targeted drugs, or some combination of the two. In the current Phase 2 study with sacituzumab govitecan, tumor shrinkage was observed in both adenocarcinoma and squamous cell carcinoma.

SCLC, which accounts for 13% of new cases, is the more aggressive form. Treatment options for SCLC are more limited, usually involve chemotherapy alone or combined with radiation. The 5-year survival rate for patients with SCLC is 6%, which is lower than that for NSCLC patients (21%).

"Advanced lung cancer is difficult to treat. We are, therefore, very encouraged by these early efficacy results," commented Cynthia L. Sullivan, President and Chief Executive Officer. "We are going to meet with regulatory authorities to formulate a registration pathway for sacituzumab govitecan first in metastatic triple-negative breast cancer, another disease with unmet needs. Meanwhile, discussions with potential partners for the out-licensing of this valuable asset are continuing," added Ms. Sullivan.

Sacituzumab govitecan continues to produce acceptable safety profile in heavily-pretreated patients, with neutropenia (24% Grades 3 and 4 combined) as the major toxicity. Diarrhea, the typical side effect of irinotecan treatment, was minimal at 3% Grade 3. More importantly, repeated efficacious doses of the ADC can be given to patients over months without evoking any interfering immune response.