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FDA fasttracking IMMUG132 for Tneg

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Topic: FDA fasttracking IMMUG132 for Tneg
Posted By: mainsailset
Subject: FDA fasttracking IMMUG132 for Tneg
Date Posted: Jan 07 2015 at 9:37pm
http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7B1f528231-9335-4c2d-af6f-1d17b6ed15a0%7D/fda-grants-fast-track-status-to-immu-132-for-triple-negative-breast-cancer" rel="nofollow - http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7B1f528231-9335-4c2d-af6f-1d17b6ed15a0%7D/fda-grants-fast-track-status-to-immu-132-for-triple-negative-breast-cancer

The first bit of the article

The FDA today granted fast track status to sacituzumab govitecan, an antibody–drug conjugate in development for treatment of patients with triple-negative breast cancer who failed prior therapies for metastatic disease, according to the drug’s manufacturer.



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Sacituzumab govitecan (IMMU-132, Immunomedics) is formed by using the moderately-toxic SN-38 — the active metabolite of irinotecan (Camptosar; Pfizer), used to treat certain solid tumors — conjugated to an anti–TROP-2 antibody.

The FDA’s Fast Track program is intended to facilitate the development and expedite the review of new drugs intended to treat serious conditions, as well as agents that would fill unmet medical needs.

The FDA based its decision on the efficacy sacituzumab govitecan has shown in patients with advanced triple-negative breast cancer.

The agent has been evaluated in patients who have undergone a median of four prior therapies (range, 1-15), including combinations of both conventional and experimental drugs.

About 30% of evaluable patients have demonstrated an objective response as measured by CT. Tumor shrinkages of 30% to 100% have been observed, according to a press release issued by Immunomedics.


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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear



Replies:
Posted By: 123Donna
Date Posted: Jan 07 2015 at 10:23pm
Mainy,

There are 2 clinical trials for IMMU-132.  One is open and the other says it has a start date of Aug 2014 (but hasn't begun recruiting).  The second one uses Carbo with Immu-132.

http://clinicaltrials.gov/ct2/show/NCT01631552?term=breast+cancer+and++IMMU-132&rank=2" rel="nofollow - http://clinicaltrials.gov/ct2/show/NCT01631552?term=breast+cancer+and++IMMU-132&rank=2

http://clinicaltrials.gov/ct2/show/NCT02161679?term=breast+cancer+and++IMMU-132&rank=1" rel="nofollow - http://clinicaltrials.gov/ct2/show/NCT02161679?term=breast+cancer+and++IMMU-132&rank=1

Our friend Beth is in the first clinical trial.  Can we begin to get excited for a breakthrough with TNBC?

DOnna


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mainsailset
Date Posted: Jan 08 2015 at 9:44am
Thanks for the links Donna, I was too lazy to go get them!
    I have such great hope for Beth in this and yes, may this finally bring the breakthrough we've all been asking for.

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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear


Posted By: tripleneg-mom
Date Posted: Jan 30 2015 at 4:07pm
Thanks for the info on IMMU-132.  Does anyone know:

 - What exactly does FDA fast track status mean?  I saw on Wikipedia that it expedites the review..., but realistically how long  does it take to get FDA approval, 5 - 7 years?

 - One of the IMMU-132 trials, the one for tnbc, shows study start date Aug, 2014, but also shows status of not yet recruiting, and no locations.  Any idea why it would be stalled?  Funding maybe? Or maybe they don't think it is needed since FDA granted fast track status and they have the other trial.

Thanks in advacne for any info - just trying to understand how this trial stuff works.  


Posted By: mainsailset
Date Posted: Jan 30 2015 at 4:15pm
From the FDA page
Fast Track Designation Request Performance
The Food and Drug Administration Modernization Act of 1997 (FDAMA) includes Section 112, "Expediting study and approval of fast track drugs." This section mandates the Agency to facilitate the development and expedite review of drugs and biologics intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Fast track adds to existing programs, such as accelerated approval, the possibility of a "rolling review" for an application. An important feature of fast track is that it emphasizes the critical nature of close early communication between the FDA and sponsor to improve the efficiency of product development.

To be eligible for the fast track program, an applicant must submit a request with supporting documentation for fast track designation for the product and its proposed use. FDA is required by the statute to decide within 60 days of receipt of the request whether the conditions for fast track designation have been met. This report illustrates CBER's performance in reviewing and deciding on these requests.

Details on the FDA fast track program, including Section 112 of FDAMA and the proposed and final rules in the Federal Register can be found in the Guidance for Industry: Expedited Programs for Serious Conditions––Drugs and Biologics - 5/20141;   Appendix 2; Appendix 3 - (CDER MAPP 6020.3); CBER SOPP 8405; Appendix 4.


--------------------------------------------------------------------------------

CBER Fast Track Designation Request Performance Report
All Requests Received
(March 1, 1998 through December 31, 2014)

Number Submitted Goal Within Goal Overdue
Granted Denied Pending Total % Granted Denied Pending Total %
304* 60 days 187 105 4 296 97 5 2 1 8 3

*Does not include three requests received by OTRR and pending on October 1, 2003. Final actions on those requests are counted in CDER reports.

http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm122932.htm#" rel="nofollow - http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm122932.htm#

Looks to me like they aim at 60 days which, for you and me, would translate into 6 months??? It all depends on how the drug has been used before, to what success, were side effects tolerable, and if there is a prior approval but for a separate disease.

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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear


Posted By: 123Donna
Date Posted: Apr 20 2015 at 11:15pm
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.


http://money.cnn.com/news/newsfeeds/articles/globenewswire/10129719.htm" rel="nofollow - http://money.cnn.com/news/newsfeeds/articles/globenewswire/10129719.htm




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Nov 08 2015 at 3:39pm
First-in-class antibody-drug conjugate shows significant clinical benefit against metastatic triple-negative breast cancer

IMMU-132, an anti-Trop-2 antibody-drug conjugate (ADC) was safe, tolerable, and yielded meaningful clinical activity in heavily pretreated patients with metastatic triplenegative  http://www.medicalnewstoday.com/articles/37136.php" rel="nofollow - breast cancer  (TNBC), according to data from a phase II clinical trial1 presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5-9.

"TNBC comprises about 15 to 20 percent of all invasive breast cancers diagnosed in the United States and is more prevalent in young and African-American women. It has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. Currently, there are no targeted treatments available for TNBC," said Aditya Bardia, MD, MPH, assistant professor of medicine at Harvard Medical School, and attending physician of medical oncology at the Massachusetts General Hospital Cancer Center in Boston.

"Trop-2 is a protein present in limited amounts in normal human tissues but widely found in many human  http://www.medicalnewstoday.com/info/cancer-oncology/" rel="nofollow - cancers . It is expressed in more than 80 percent of TNBC, making it an attractive therapeutic target," Bardia added. Sacituzumab govitecan (IMMU-132) is a first-in-class ADC, which was developed by linking approximately eight molecules of SN-38 (an active metabolite of the  http://www.medicalnewstoday.com/articles/158401.php" rel="nofollow - chemotherapy  agent irinotecan) to an antibody that binds to Trop-2, he explained.

"Patients treated with other agents used to treat heavily pretreated metastatic TNBC have a median progression-free survival [PFS] of three to four months in general, while in our phase II clinical trial, patients on IMMU-132 had an interim median PFS of seven months. The response rate to standard agents is usually 10 to 20 percent, while the response rate with IMMU-132 was approximately 30 percent. If you include patients with stable disease, the clinical disease control rate, which is complete response [CR] + partial response [PR] + stable disease, was about 75 percent. Two patients had a CR to treatment, something which is rarely seen in patients with heavily pretreated metastatic TNBC," Bardia said.

"We hope that this drug can be further developed and, if approved, provide a significantly better alternative for these patients with poor prognosis," Bardia said. IMMU-132 received Fast Track designation2 from the U.S. Food and Drug Administration for the treatment of patients with TNBC, he added.

As of October 2015, Bardia and colleagues had enrolled in the multicenter phase II trial 83 TNBC patients who had not responded to previous treatments or had relapsed after successful treatment. The first patient was enrolled into this study 31 months ago. All patients received IMMU-132 once a week for 2 weeks followed by one week of rest. This treatment cycle was repeated until the patient had disease progression or withdrew from the trial. Patients were evaluated for safety every week and assessed for response every two months.

For the 54 patients with 2 or more prior lines of treatment that included a taxane who had received IMMU-132 at the 10 mg/kg dose level, the overall response rate, defined as CR plus PR, was 31.5 percent, and included two CRs.

"One of the most interesting findings is that the agent was well tolerated by patients, and toxicity was much lower than one would anticipate with chemotherapy agents such as irinotecan," Bardia said. Grade 3 to 4 toxicities included neutropenia (in 15 percent of the patients),  http://www.medicalnewstoday.com/articles/158800.php" rel="nofollow - anemia  (6 percent),  http://www.medicalnewstoday.com/articles/158634.php" rel="nofollow - diarrhea  (6 percent), and febrile neutropenia (4 percent), and no patient discontinued treatment because of toxicity issues.

Twenty-two patients continue to receive treatment, and the overall survival data are not yet mature, with 87 percent of patients still alive, Bardia noted.

http://www.medicalnewstoday.com/releases/302233.php?tw" rel="nofollow - http://www.medicalnewstoday.com/releases/302233.php?tw



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Feb 07 2016 at 11:19pm
FDA Grants Antibody-Drug Conjugate Breakthrough Designation in TNBC 

http://www.onclive.com/web-exclusives/fda-grants-antibody-drug-conjugate-breakthrough-designation-in-tnbc" rel="nofollow - http://www.onclive.com/web-exclusives/fda-grants-antibody-drug-conjugate-breakthrough-designation-in-tnbc


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 06 2016 at 9:21pm
Data Intriguing for Sacituzumab Govitecan (IMMU-132) in TNBC 

Sacituzumab govitecan (IMMU-132) had an objective response rate (ORR) of 33% in pretreated patients with triple-negative breast cancer (TNBC), according to updated findings from a phase II study reported by Immunomedics, the manufacturer of the antibody-drug conjugate.

The results were originally scheduled to be presented at the 2016 ASCO Annual Meeting; however, the study was excluded from the conference when ASCO became aware that its meeting embargo had been violated when the chairman of Immunomedics reported the results at a conference in April. The ASCO exclusion did not question the quality of the research findings, according to a statement from Immunomedics.

“Both we and our many investigators involved are disappointed that our excellent therapeutic results, achieving an interim median survival of about 14 months, may not be presented at this meeting. These results are very encouraging for TNBC patients with metastatic disease who failed multiple prior therapies,” Cynthia L. Sullivan, president and CEO of Immunomedics, said in a statement.

In the phase II study, 60 patients with metastatic TNBC received either 8 or 10 mg/kg of sacituzumab govitecan intravenously on days 1 and 8 of 21-day repeated cycles. The median number of doses was 8 (range, 1-37). Patients had progressed on at least 2 prior treatments, including a taxane. Seventy percent of patients had an ECOG performance status of 1, with the remaining 30% having an ECOG performance of 0. The median age was 54 years (range, 31-80 years).

The median number of prior therapies was 5 (range, 2-12). Prior treatments received included cyclophosphamide (93%), doxorubicin (83%), carboplatin (57%), gemcitabine (50%), capecitabine (43%), eribulin (38%), cisplatin (25%), vinorelbine (17%), and bevacizumab (13%).

As of May 2016, the ORR was 33%, with a confirmed ORR of 28% and a median duration of response of nearly 11 months. The median progression-free survival was 5.6 months and the median overall survival was 14.3 months.

Safety data for these these patients with a cutoff date of November 10, 2015 were previously reported in December at the 2015 San Antonio Breast Cancer Symposium.1 The most common all-grade adverse events (AEs) in the 10 mg/kg arm were diarrhea (27%), nausea (27%), neutropenia (23%), vomiting (22%), alopecia (18%), anemia (17%), fatigue (17%), constipation (13%), rash (13%), and abdominal pain (10%).

The most frequently reported grade ≥3 AEs in the 10 mg/kg cohort were neutropenia (15%), leukopenia (8%), diarrhea (5%), fatigue (3%), dyspnea (3%), febrile neutropenia (2%), and anemia (2%).

Based on data from the phase II study, sacituzumab govitecan received an FDA breakthrough therapy designation in February 2016 for the treatment of patients with TNBC following at least 2 treatments for metastatic disease. Immunomedics plans to submit an application to the FDA for accelerated approval of sacituzumab govitecan in this setting based on the ongoing phase II trial. The company also plans to launch a confirmatory phase III trial by the end of the 2016, and will publish the phase II study data in a peer-reviewed journal.

http://www.onclive.com/web-exclusives/despite-asco-mishap-data-still-intriguing-for-sacituzumab-govitecan-in-tnbc" rel="nofollow - http://www.onclive.com/web-exclusives/despite-asco-mishap-data-still-intriguing-for-sacituzumab-govitecan-in-tnbc




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 14 2016 at 8:03am
University of Colorado Cancer Center researcher Jennifer Diamond, MD, is an investigator on three clinical trials of targeted therapies against triple-negative breast cancer (TNBC), two of which were presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2016 and one of which was presented just prior to the meeting. Each therapy uses a distinct strategy influenced by the immune system and all three have real potential to extend the lives of women whose cancers have progressed after previous treatments. . .

. . .The first study, presented before ASCO, reports the phase I/II clinical trial of the drug IMMU-132, which was recently granted “breakthrough” status by the FDA, meant to speed the approval of the most promising new drugs. IMMU-132 is an “antibody-drug conjugate” meaning that it is, in fact, two distinct pieces linked together. In this case, the drug is a molecule related to the chemotherapy irinotecan. And the antibody is a molecule that binds to the protein Trop2, which is overexpressed in about 80 percent of all TNBC.

“The strategy is to use this Trop2 antibody to help the chemotherapy find and target the disease,” Diamond says.

The approach is similar to the mechanics of the immune system in which an antibody recognizes the surface proteins of a bacterium or virus and then directs a T cell to target invaders. (Only, in the case of this antibody-drug conjugate, irinotecan replaces the T cell as the agent responsible for killing unwanted cells.)

Sixty TNBC patients treated with IMMU-132 had an average of five prior rounds of therapy, meaning that their heavily pretreated cancers had proven especially resistant to therapy. In this notoriously difficult group, the overall response rate was 33% and the median duration of response was nearly 11 months. Six months later, 48 percent of patients’ tumors remained stable or better, with one complete response, meaning that after treatment, this woman’s aggressive breast cancer became undetectable.

http://www.coloradocancerblogs.org/asco-finally-targeted-therapy-triple-negative-breast-cancer/" rel="nofollow - http://www.coloradocancerblogs.org/asco-finally-targeted-therapy-triple-negative-breast-cancer/




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mainsailset
Date Posted: Jun 14 2016 at 6:30pm
Thanks for the update Donna. Sounds like the trials are proving fruitful. To take a group of Tneg's that is already demonstrating resistance to conventional and get a 33% good result may not seem like success to those new to the fight but it is indeed impressive. More please!

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dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear


Posted By: 123Donna
Date Posted: Mar 27 2017 at 12:19pm

30% of Aggressive Breast Cancer Patients Respond to Sacituzumab Govitecan, Trial Shows

Thirty percent of patients with metastatic triple-negative breast cancer (TNBC) responded to the experimental therapy sacituzumab govitecan after failing to respond to other treatments, according to Phase 2 trial results.

Other measures of its effectiveness included the length of time patients responded to treatment, overall patient survival rate, and time to progression. The therapy was also well-tolerated, the team added.

The study, “ http://ascopubs.org/doi/10.1200/JCO.2016.70.8297" rel="nofollow - Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer ,” was published in the  http://ascopubs.org/journal/jco" rel="nofollow - Journal of Clinical Oncology .

Sacituzumab govitecan is an antibody-drug conjugate composed of an anti-TROP-2 antibody linked to a toxic payload, SN-38.

To read more:
http://breastcancer-news.com/2017/03/21/aggressive-breast-cancer-therapy-shows-promise-in-clinical-trail" rel="nofollow - http://breastcancer-news.com/2017/03/21/aggressive-breast-cancer-therapy-shows-promise-in-clinical-trail



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 07 2019 at 8:28pm

Phase 3 Trial of Sacituzumab Govitecan Recruiting Triple-negative Breast Cancer Patients

A Phase 3 trial is recruiting participants to examine the effects of sacituzumab govitecan in patients with metastatic  http://breastcancer-news.com/tag/triple-negative-breast-cancer/" rel="nofollow - triple-negative breast cancer  (TNBC) who failed to respond, or relapsed after at least two prior treatments.

Patients are being https://clinicaltrials.gov/ct2/show/study/NCT02574455#contacts" rel="nofollow - recruited for the trial ( https://clinicaltrials.gov/ct2/show/NCT02574455" rel="nofollow - NCT02574455 ) across several clinical sites in the United States, Canada, France, Belgium, Spain, the United Kingdom, and Germany. Participating centers in the U.S. can be found http://tnbctrial.com/?gclid=Cj0KCQiA3b3gBRDAARIsAL6D-N_OSNhP-2FLXebWccmyitTIR1APKd2JgKOwVBYk9hToFDNRQeCsmxUaAmtiEALw_wcB" rel="nofollow - here .

https://breastcancer-news.com/2019/01/04/phase-3-trial-sacituzumab-govitecan-recruiting" rel="nofollow - https://breastcancer-news.com/2019/01/04/phase-3-trial-sacituzumab-govitecan-recruiting



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




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