On August 3, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported the establishment of the Immuno-Oncology Rare Population Malignancy (I-O RPM) program in the U.S (Press release, Bristol-Myers Squibb, AUG 3, 2015, View Source [SID:1234506979]).

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The I-O RPM program is a multi-institutional initiative with academic-based cancer centers focused on the clinical investigation of Immuno-Oncology therapeutics as potential treatment options for patients with high risk, poor prognostic cancers, defined as a rare population malignancy. A rare population malignancy is a subpopulation within a higher incident disease population (e.g. BRCA 1 and 2 breast cancer). These patients have aggressive disease with an increased potential for early metastasis to multiple sites and/or are initially refractory or subject to early recurrences with conventional cancer therapies.

As part of the I-O RPM program, Bristol-Myers Squibb, the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (Lurie Cancer Center) and the Northwestern Medicine Developmental Therapeutics Institute (NMDTI) are pleased to announce that they have entered into a collaboration agreement. The Lurie Cancer Center and NMDTI will conduct a range of early phase clinical studies and Bristol-Myers Squibb will fund positions within the NMDTI Developmental Therapeutics Fellowship program.

"Complementing our broad research and development programs through innovative collaborations with partners such as the Lurie Cancer Center and NMDTI has been a fundamental component to our commitment to leading advances in Immuno-Oncology," said Laura Bessen, M.D., head of U.S. Medical, Bristol-Myers Squibb. "Cooperation between industry and research partners of this caliber offers a tremendous opportunity to further strengthen our scientific and clinical understanding of the role immunotherapies can play in the treatment of a broad range of cancers."

"Immunotherapy is rapidly evolving and has an enormous promise for cancer patients. This collaborative effort with Bristol-Myers Squibb will further strengthen our efforts to develop innovative new therapies against a wide variety of malignancies," said Leonidas C. Platanias, M.D., Ph.D., director of the Lurie Cancer Center.

"The Rare Population Malignancy Program is a very timely and important initiative. The ability to rapidly investigate the clinical utility of Bristol-Myers Squibb’s Immuno-Oncology agents, as single agents or in combinations, including with therapies from other sources, is a powerful accelerant to our programs. The focus on malignancies that are otherwise relatively under-investigated in therapeutic terms is particularly important and satisfying for all involved in this collaboration," said Francis J. Giles, M.D., director of the NMDTI and deputy director of the Lurie Cancer Center.

Immuno-Oncology is an innovative approach to cancer research and treatment that is designed to harness the body’s own immune system to fight cancer. The I-O RPM program will focus on significant areas of high unmet need marked by poor outcomes among patients with these cancers. Existing clinical research, including studies being conducted by the Lurie Cancer Center and NMDTI, provide a strong rationale for further research into the potential of immunotherapies for these cancers.

On August 3, 2015 Ipsen (Euronext: IPN; ADR: IPSEY) reported that its partner, Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), disclosed positive results from the pivotal Phase 3 TELESTAR study (Press release, Ipsen, AUG 3, 2015, View Source [SID:1234506977]). TELESTAR evaluated the efficacy and safety of telotristat etiprate for carcinoid syndrome patients with metastatic neuroendocrine tumor (NET) inadequately controlled by somatostatin analog (SSAs), the current standard of care.

Top-line results from the Phase 3 study show that patients who added telotristat etiprate to the standard of care at both the 250 mg and 500 mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint. Complete results from the Phase 3 TELESTAR study will be presented at an upcoming scientific conference. Claude Bertrand, Executive Vice President R&D and Chief Scientific Officer, Ipsen stated: "We are pleased with the positive top-line Phase 3 results for telotristat etiprate. Should telotristat etiprate be approved, its oral formulation would satisfy an unmet medical need for patients with carcinoid syndrome not adequately controlled with SSAs therapy. After the approval of Somatuline Autogel as the first and only SSA for tumor control of gastro-intestinal and pancreatic neuroendocrine tumors (NETs) in the US and Europe, and the more recent acquisition of Octreopharm’s nuclear medicine platform, these results are an important milestone in our strategy to become a global leader in NETs." Professor Marianne Pavel, Charité-Universitätsmedizin Berlin, Principal Investigator, study lead in Germany stated: "There is a need for effective treatment to improve the health and comorbidities of patients whose carcinoid syndrome is not adequately controlled with somatostatin analogue therapy. Results of this positive phase 3 study with telotristat etiprate are promising in improving symptom management, and outcome of patients with carcinoid syndrome not adequately controlled with SSA therapy". In October 2014, Ipsen and Lexicon announced that they had entered into an exclusive licensing agreement for Ipsen to commercialize telotristat etiprate, excluding the US and Japan, with a focus on the symptomatic treatment of carcinoid syndrome inadequately controlled with SSAs. Lexicon retains sole rights to commercialize telotristat etiprate in the United States and Japan. About the study The double-blind Phase 3 study known as TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) enrolled 135 patients with carcinoid syndrome who were not adequately controlled on SSA therapy, the current standard of care. The three-arm study evaluated two doses of oral telotristat etiprate – 250 mg and 500 mg, each taken three times daily – against placebo over a 12-week period and measured the reduction from baseline in the average number of daily bowel movements. Patients in both the treatment and placebo arms continued their SSA therapy throughout the study. Top-line results from TELESTAR show that patients who added telotristat etiprate to SSA therapy at both the 250 mg and 500 mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint. In another key finding, a substantially greater proportion of patients on telotristat etiprate achieved a durable response (44 percent and 42 percent in the 250 mg and 500 mg arms, respectively), defined as at least a 30 percent reduction in daily bowel movements over at least half the days of the study period, as compared to 20 percent response on placebo (p<0.040). Patients who received 250 mg of telotristat etiprate experienced a 29 percent reduction in the average number of daily bowel movements during the final week (week 12) of the study period compared to baseline, and those in the 500 mg arm had a 35 percent reduction, while the placebo group showed a 17 percent reduction. These results are consistent with those seen in the 12-week Phase 2 study of telotristat etiprate. The proportion of patients with treatment-emergent adverse events (AEs), serious AEs and discontinuation due to AEs were generally similar in all three treatment arms. The tolerability profile of telotristat etiprate 250 mg tid appeared similar to placebo and somewhat better than 500 mg tid with respect to gastrointestinal discomfort and mood. Further in depth analysis of safety and tolerability data will be conducted. The 12-week double-blind study period is being followed by a 36-week open-label extension where all patients receive telotristat etiprate 500 mg three times daily.

On August 3, 2015 lovis Oncology, Inc. (NASDAQ: CLVS) reported that it has submitted its New Drug Application (NDA) regulatory filing to the U.S. Food and Drug Administration (FDA) for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA approved test (Press release, Clovis Oncology, AUG 3, 2015, View Source [SID:1234506974]).

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Rociletinib is the Company’s novel, oral targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Rociletinib was granted Breakthrough Therapy designation by the U.S. FDA in May 2014.

In addition, Clovis has also submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) through the centralized procedure for rociletinib for the treatment of adult patients with mutant EGFR NSCLC who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation.

There is a validation period before both applications are formally accepted, after which the review commences.

"The submissions of our first NDA and MAA for rociletinib represent a major step forward for our company," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "These two submissions – completed on the same day, no less — were made possible through the tremendous commitment and hard work of Clovis employees and our clinical collaborators at leading U.S. and international academic institutions over the last many months, and I am grateful for their tireless efforts. We are actively preparing for what we hope to be our first U.S. commercial launch, and the opportunity to address the needs of patients with T790M-positive EGFR-mutant non-small cell lung cancer. We are also actively building our commercial organization in Europe to prepare for a potential launch next year."

QIAGEN, Clovis’ companion diagnostic partner, intends to file a supplemental PMA application of its approved therascreen EGFR test with the FDA to allow for regulatory approval of the companion diagnostic concurrent with rociletinib approval. Analytical performance of the therascreen EGFR test has been established for 21 EGFR mutations, including the most prevalent resistance mutation, T790M. The test supports efficient laboratory workflow with real-time PCR technology on the FDA approved Rotor-Gene Q MDx, which is part of QIAGEN’s QIAsymphony family of laboratory solutions.

About Rociletinib

Rociletinib is an oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Rociletinib targets the activating mutations of EGFR (L858R and Del19), while also inhibiting the dominant acquired resistance mutation, T790M, which develops in approximately 60 percent of patients treated with first- and second-generation EGFR inhibitors, while sparing wild-type, or "normal" EGFR at anticipated therapeutic doses. Accordingly, it has the potential to treat NSCLC patients with EGFR mutations both as a first-line or second-line treatment. Rociletinib was granted Breakthrough Therapy designation by the U.S. FDA in May 2014.

About Rociletinib Clinical Development

Clovis has several studies underway in EGFR-mutant NSCLC:

TIGER-X is a Phase 1/2 study designed to evaluate the safety and efficacy of three different doses of rociletinib in a very advanced patient population.

TIGER-1 is a randomized Phase 2/3 registration study versus erlotinib in newly-diagnosed patients.

TIGER-2 is a global registration study in both T790M-positive and T790M-negative patients directly after progression on their first and only TKI therapy.

TIGER-3 is a randomized, comparative study versus chemotherapy in both T790M-positive and T790M-negative patients with acquired TKI resistance.

A Phase 1 study of rociletinib in Japan has completed enrollment and a Phase 2 study in Japanese patients, agreed upon with Japanese regulatory authorities, is expected to initiate in the second half of 2015.

Multiple combination studies are planned to initiate in the second half of 2015, including inhibitors of PD-L1, PD-1 and MEK.
For more information, please visit www.tigertrials.com.

About Lung Cancer and EGFR Mutations

Lung cancer is the most common cancer worldwide with 1.35 million new cases annually, with NSCLC accounting for almost 85 percent of all lung cancers. NSCLC progresses rapidly with a five-year survival rate in advanced NSCLC patients of less than five percent. EGFR activating mutations occur in approximately 10 to 15 percent of NSCLC cases in Caucasian patients and approximately 30 to 35 percent in East Asian patients. These patients often experience significant tumor response to erlotinib, afatinib and gefitinib, which are first- and second-generation EGFR inhibitors. However, most patients ultimately progress on these therapies, with approximately 60 percent of patients developing acquired resistance from a second, "gatekeeper" mutation, T790M. Currently, no targeted therapies are approved for treatment of this mutation.