On December 10, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported the presentation of the study design and a trial update for a Phase 1b/2 study of Ad-RTS-hIL-12 + veledimex following standard chemotherapy for the treatment of patients with locally advanced or metastatic breast cancer (Press release, Ziopharm, DEC 10, 2015, View Source [SID:1234508528]). The poster presentation, titled "Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer," was presented as part of the "Ongoing Trials – Immunotherapy" session of the 2015 San Antonio Breast Cancer Symposium, and is available online at www.ziopharm.com.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study, which is being conducted at the Memorial Sloan Kettering Cancer Center in New York and began enrollment in June 2015, is designed to examine the safety, tolerability and efficacy of Ad-RTS-hIL-12 immunotherapy in up to 40 women with locally advanced or metastatic breast cancer of all subtypes. Ad-RTS-hIL-12 + veledimex is a novel gene therapy which controls local expression of IL-12 and may induce tumor stroma collapse and stimulation of an anti-cancer T cell immune response. The ability to regulate the production of IL-12 by modulating veledimex dosing is designed to improve its therapeutic index with standard of care.

Following entry into the trial, patients go on a chemotherapy holiday and enter an immunotherapy phase of treatment. A single cycle of Ad-RTS-hIL-12, along with the oral activator ligand veledimex, is given during the immunotherapy phase, with the goal of maintaining or improving pre-study response. Continuation of HER2-targeted antibody therapy is permitted during this immunotherapy phase for women with HER2+ disease. The study design allows for a review of the trial after every five subjects with HER2‑ and with HER2+ disease are treated. To date, five patients have been enrolled, including four with HER2- disease and one with HER2+ disease.

"Following standard of care treatment with an immunotherapy has the potential to deliver a one-two punch in breast cancer, particularly in a setting where IL-12, a potent immune cytokine, has demonstrated profound effects on the tumor environment," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We are pleased to see patient enrollment in this study accelerating and, beginning in 2016, look forward to understanding how the promise of this approach translates into outcomes."

On December 10, 2015 Seattle Genetics, Inc. (Nasdaq: SGEN) reported data from an ongoing phase 1 clinical trial evaluating SGN-LIV1A, an antibody-drug conjugate (ADC) in development for patients with LIV-1-expressing metastatic breast cancer (MBC), at the 38th San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas, December 8-12, 2015 (Press release, Seattle Genetics, DEC 10, 2015, View Source;p=RssLanding&cat=news&id=2121626 [SID:1234508527]). SGN-LIV1A consists of a humanized anti-LIV-1 monoclonal antibody (mAb) and the microtubule-disrupting agent monomethyl auristatin E (MMAE), utilizing a protease-cleavable linker. ADCs are monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"While there have been important advances in the treatment of breast cancer, there remains a significant unmet medical need for improved therapies, particularly in the metastatic setting where there are no curative therapies and fewer than 25 percent of patients survive five years," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "The data presented at SABCS on SGN-LIV1A demonstrate early antitumor activity in heavily pretreated patients, notably among patients with triple negative disease, at generally well-tolerated doses. We are currently enrolling patients with triple negative breast cancer, a subtype for which there are no approved targeted treatments available, to further assess the activity of SGN-LIV1A in a disease-specific cohort."

Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-LIV1A in Patients with Metastatic Breast Cancer (Abstract #638, Poster Session 3 at 5:00 – 7:00 p.m. CT on Thursday, December 10, 2015)

LIV-1 is highly expressed in breast cancer, and is present in 96 percent of 237 MBC samples screened to date. Moderate-to-high expression was observed in 88 percent of hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancers and in 79 percent of triple negative breast cancers (TNBC). The ongoing phase 1, open-label, dose-escalation trial is evaluating the safety, tolerability, antitumor activity, pharmacokinetics and maximum tolerated dose (MTD) of SGN-LIV1A monotherapy administered every three weeks in patients with LIV1-expressing MBC.

Data were reported from 27 patients with LIV-1-expressing MBC, of whom 18 were HR+/HER2- and nine were TNBC. The median age of patients was 57 years and the median number of prior systemic metastatic cytotoxic therapies was four. Key findings presented by Dr. Andres Forero, from the University of Alabama at Birmingham, included:

Of the 25 efficacy-evaluable patients, the objective response rate (ORR) was 12 percent, the disease control rate was 64 percent and the clinical benefit rate (CBR) was 24 percent. Disease control rate is defined as patients achieving a complete response (CR), partial response (PR) or stable disease (SD). CBR is defined as patients achieving CR, PR or SD lasting at least six months.
Among the eight patients with TNBC, the ORR was 38 percent and CBR was 63 percent.

At the time of data analysis, early estimates of median progression-free survival (PFS) for all patients was 11 weeks, with an estimated median PFS in TNBC patients of 18.4 weeks and an estimated median PFS in HR+/HER2- patients of 11.3 weeks.
The most common of the adverse events (AEs) of any grade occurring in 15 percent or more of patients included nausea (52 percent), fatigue (48 percent), alopecia and peripheral neuropathy (44 percent each) and decreased appetite and vomiting (33 percent each). There was a low incidence of myelosuppression, with grade 3 or 4 adverse events of neutropenia in 19 percent of patients and anemia in 11 percent of patients. Grade 3 peripheral neuropathy occurred in 11 percent of patients.

The MTD was not reached among doses ranging from 0.5 to 2.8 milligrams per kilogram (mg/kg). Dose escalation is complete.
Enrollment in a TNBC expansion cohort is ongoing.

More information about the SGN-LIV1A phase 1 clinical trial, including enrolling centers, is available by visiting www.clinicaltrials.gov.

About SGN-LIV1A

SGN-LIV1A is an ADC that combines a humanized anti-LIV-1 monoclonal antibody linked to a synthetic cytotoxic cell-disrupting agent, monomethyl auristatin E (MMAE). The ADC is designed to bind to LIV-1 proteins, which are expressed in most subtypes of metastatic breast cancer, and to release the potent cytotoxic agent MMAE into the target cell upon internalization into LIV-1-expressing tumor cells. This approach is intended to spare non-targeted cells and may reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity.

About Breast Cancer

While there are several therapies available or in development for breast cancer, there remains a significant need to identify improved treatment options. Breast cancer is a disease where malignant (cancer) cells form in the tissue of the breast. Metastatic breast cancer occurs when the cancer has spread to other parts of the body. Breast cancer is the most common cancer, excluding non-melanoma skin cancer, and the second leading cause of cancer death in women. The American Cancer Society estimates that more than 234,000 new cases of breast cancer will be diagnosed in the United States in 2015, and more than 40,000 people will die from the disease. While most new diagnoses of breast cancer are made at an early stage, approximately one-third of these patients will eventually develop recurrent or metastatic disease.

On December 10, 2015 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates, including both cellular immunotherapy and checkpoint inhibitor platforms, to improve the lives of patients with cancer, reported the presentation of preliminary safety data from NLG2101, a randomized Phase 2 trial evaluating an IDO pathway inhibitor indoximod in combination with taxane-based chemotherapy for patients with breast cancer (Press release, NewLink Genetics, DEC 10, 2015, View Source [SID:1234508525]). The data were presented today at the 2015 San Antonio Breast Cancer Symposium.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

NLG2101 is a randomized, double-blind, placebo-controlled Phase 2 trial of indoximod 1200 mg orally, twice daily in combination with docetaxel 75 mg/m2 every 3 weeks or paclitaxel 80 mg/m2 weekly in patients with metastatic ER/PR positive or negative, HER2 negative breast cancer. The trial, which reached its goal of 154 patients enrolled across multiple sites in the United States and Europe, is designed to evaluate the combination of indoximod and chemotherapy as first-line therapy for patients with metastatic breast cancer. The study’s primary endpoint is progression-free survival, with secondary endpoints of overall survival, response rate per RECIST 1.1 criteria, safety, and immune response correlative assays.

Preliminary evaluable safety data from 128 patients, when considered in a blinded fashion pooling control and treatments arms of the study, suggests that the regimen is generally well tolerated. The addition of indoximod to standard of care chemotherapy for metastatic breast cancer did not increase expected adverse events known to be associated with the administered chemotherapies. Additionally, no unexpected safety signals were reported with the combination of indoximod with docetaxel or paclitaxel, suggesting that there is no additional or unique toxicity with the addition of indoximod to chemotherapy.

Objective responses were achieved in an earlier Phase 1 trial combining indoximod and docetaxel in patients with metastatic solid tumors, including breast tumors.

"I believe this is an exciting chemoimmunotherapy combination regimen for patients with metastatic breast cancer," said Shou-Ching Tang, M.D., Ph.D., Professor of Medicine, Leader, Breast Cancer Multidisciplinary Team at Augusta University. "These data suggest that indoximod may become a valuable addition to standard breast cancer treatment regimens due to the potential for enhancing a patient’s immune system to fight cancer without additive toxicity. I eagerly await the full results of this trial evaluating a promising immune check point inhibitor in combination with chemotherapy."

The data, presented during the poster session "Treatment: Immunotherapy," correspond to the abstract (P2-11-09) entitled, "A phase 2 randomized trial of the IDO pathway inhibitor indoximod in combination with taxane based chemotherapy for metastatic breast cancer: preliminary data."

Indoximod is an orally available small molecule that has shown the potential to interfere with multiple targets within the indoleamine 2,3-dioxygenase (IDO) pathway. It is designed to be used in combination with other therapeutic agents to maximize the body’s immune response against a range of tumor types. Indoximod is currently in multiple Phase 2 clinical trials for the treatment of patients with breast, prostate, pancreatic, melanoma and brain cancers and in Phase 1 clinical trials for the treatment of pediatric patients with primary malignant brain tumors.

On December 10, 2015 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that new data will be presented demonstrating the role of the myChoice HRD companion diagnostic in identifying patients with breast cancer who are likely to respond to a platinum-containing therapy (Press release, Myriad Genetics, DEC 10, 2015, View Source [SID:1234508523]). The data will be presented at the 2015 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"There is mounting clinical evidence demonstrating the ability of myChoice HRD to identify patients who experience improved outcomes when treated with platinum-containing therapy," said Anne-Renee Hartman, M.D., vice president of clinical development, Myriad Genetic Laboratories. "Our collaborators will present data showing how this test might be useful to optimize therapy selection for patients. The data underscore the critical importance of identifying patients at the time of diagnosis who are likely to benefit from a therapeutic response to platinum prior to surgery. These findings support earlier studies showing that myChoice HRD gives the most complete picture of clinical response to platinum-containing chemotherapy."

Details about the featured myChoice HRD presentations at SABCS are below. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #SABCS15.

myChoice HRD Presentations

Title: Homologous recombination deficiency (HRD) as a predictive biomarker of response to neoadjuvant platinum-based therapy in patients with triple negative breast cancer (TNBC); A pooled analysis.
Date: Thursday, Dec.10, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster P3-07-12.
Presenter: Dr. Melinda Telli, Stanford University Cancer Center.

A pooled analysis of five Phase II trials that included patients with TNBC treated with neoadjuvant platinum-based chemotherapy was conducted to evaluate the pathologic complete response (pCR) rates in homologous recombination (HR) deficient and HR non-deficient tumors. HR deficiency status was defined as either a positive myChoice HRD score (42 or higher) or presence of a BRCA1/2 tumor mutation (tBRCA). The results of this analysis with 267 patients showed that myChoice HRD predicted pCR in TNBC across several different platinum-based chemotherapy regimens. Specifically, patients with a positive myChoice HRD score had a five-fold increase in pCR compared to those with negative score.

Title: Homologous recombination deficiency (HRD) as a predictive biomarker of response to preoperative systemic therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer.
Date: Thursday, Dec.10, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster P3-07-13.
Presenter: Dr. Roisin Connolly, Johns Hopkins School of Medicine.

This study assessed the ability of myChoice HRD to predict pathological complete response (pCR) in 48 patients with ER-positive or triple negative breast cancer who were treated with PST comprising a platinum drug. In the analysis of all patients, the results showed a significantly higher pCR rate in patients with a positive myChoice HRD score than a negative score (50 percent vs 8 percent, p=0.002). A similar trend was observed for both ER-positive and TNBC patients. In a subgroup analysis of patients without a tBRCA mutation (n=40), there was a significantly higher pCR rate in patients with a positive myChoice HRD score than a negative score (64 percent vs 8 percent, p≤0.001). These results show that myChoice HRD predicts response to a platinum-containing chemotherapy regimen in the estimated 15 percent of newly diagnosed breast cancer patients with TNBC. Furthermore, this is the first study to show that myChoice HRD may be useful in predicting response to platinum-containing chemotherapy regimens in patients with ER-positive, Her2-negative breast cancer, which represents approximately 70 percent of newly diagnosed breast cancer patients.

For more information about these presentations, please visit the SABCS website at View Source

About myChoice HRD

Myriad’s myChoice HRD is the first homologous recombination deficiency test that can detect when a tumor has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. High myChoice HRD scores reflective of DNA repair deficiencies are prevalent in all breast cancer subtypes, ovarian and most other major cancers. In previously published data, Myriad showed that the myChoice HRD test predicted drug response to platinum therapy in certain patients with triple-negative breast and ovarian cancers. It is estimated that 1.8 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents.