On October 19, 2018 QED Therapeutics reported the presentation of positive, reported that updated interim data of infigratinib (BGJ398), an orally administered, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, for the treatment of advanced or metastatic cholangiocarcinoma (bile duct cancer) during a late-breaking poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) (Press release, QED Therapeutics, OCT 19, 2018, View Source [SID1234576273]).

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!

In the open-label trial, which enrolled 71 patients with FGFR2 fusions/translocations, the confirmed overall response rate (cORR) was 26.9% (95% CI 16.8-39.1%) for all patients with the potential for confirmation (n=67) and an additional 56.7% experienced stable disease as their best response, resulting in a disease control rate of 83.6%. For patients who had received one or fewer prior treatment regimens, the cORR was 39.3% (n=28), whereas patients who had received two or more treatment regimens had a cORR of 17.9%. Median progression free survival was 6.8 months (95% CI 95% CI 5.3-7.6) and median overall survival was 12.5 months (95% CI 9.9-16.6 months).

"These updated data provide the most extensive experience for an FGFR inhibitor in advanced cholangiocarcinoma," said Milind Javle, M.D., professor, gastrointestinal medical oncology, The University of Texas MD Anderson Cancer Center and investigator on the Phase 2 infigratinib (BGJ398) study. "The high disease control rate and impressive overall survival are promising in a disease with no currently approved targeted treatments."

"These results show that infigratinib has strong potential to make a real difference in the lives of people with cholangiocarcinoma," said Susan Moran, M.D., M.S.C.E., chief medical officer of QED Therapeutics. "Importantly, we have initiated a pivotal, Phase 3 study in first-line cholangiocarcinoma in the hopes of offering patients an upfront chemotherapy-free treatment option."

The study also demonstrated that infigratinib-associated toxicity is manageable. Most common treatment-emergent adverse events (TEAE) were hyperphosphatemia (73.2%), fatigue (49.3%), stomatitis (45.1%), alopecia (38.0%) and constipation (35.2%). Grade 3/4 TEAEs occurred in 47 patients (66.2%), including hypophosphatemia (14.1%), hyperphosphatemia (12.7%) and hyponatremia (11.3%).

Cholangiocarcinoma affects approximately 8,000 to 10,000 patients a year in the United States. Currently, treatment options are limited, and survival rates are generally poor.

FGFR alterations have been implicated as an oncogenic driver across multiple solid tumors and hematological cancers – including roughly one out of every five cases of cholangiocarcinoma and urothelial carcinoma. Activating mutations in FGFRs are also found in multiple forms of pediatric skeletal dysplasias, including achondroplasia, which affects up to one out of every 15,000 live births.

A Phase 3 study comparing infigratinib to standard of care chemotherapy for first line cholangiocarcinoma has been initiated by QED Therapeutics

On October 19, 2018 Menarini Ricerche reported the initiation of the B-PRECISE-01 clinical trial, a multicenter phase Ib study that will evaluate the safety and efficacy of MEN1611 plus trastuzumab with or without fulvestrant (Press release, Menarini, OCT 19, 2018, View Source [SID1234531253]). The study will enroll patients with PIK3CA-mutated, HER2-positive, advanced or metastatic (a/m) breast cancer who have failed anti-HER2 based therapy. MEN1611 is a potent, selective, orally available class I PI3k inhibitor showing high activity against p110α mutant isoforms, and minimal inhibition of the δ isoform. The compound has been in-licensed by Menarini from Chugai Pharmaceuticals in Nov 2016 after the successful completion of the FIH study (PA-799EU), which showed a promising safety profile.

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!

Menarini, in collaboration with a broad network of oncology centers of excellence, including the Memorial Sloan–Kettering Cancer Center (New York, USA) and the Vall d’Hebron Institute of Oncology (Barcelona, Spain), has conducted additional, extensive preclinical investigations using multiple animal models. In these experiments, MEN1611 as single agent and in combination showed anti-tumor activity against a panel of solid cancers where the PI3k mutation has an important, negative impact on prognosis and response to treatment.

The B-PRECISE-01 study of MEN1611 will be conducted in major European oncology sites in Italy, Spain, Belgium, France, UK and The Netherlands. The study is designed to identify the optimal dose of MEN1611 to be administered in combination with trastuzumab with or without fulvestrant, and to collect preliminary evidence of clinical activity in patients with a/m Her2-positive breast cancer. While the B-PRECISE-01 study is on-going, Menarini is committed to expand the clinical investigation of MEN1611 in breast cancer as well as in other solid tumors with high medical need, where PIK3CA represents a suitable therapeutic target.

"Focusing on targeted therapies that can be developed based on precision medicine approaches is a key component of the Menarini strategy in oncology" said Andrea Pellacani, MD,PhD, General Manager of Menarini Ricerche "The design of the B-PRECISE-01 study focused on a sub-group of patients with high unmet need and selected on the basis of the specific mechanism of action of MEN1611 is completely aligned with our strategy, and strongly confirms our commitment to oncology and precision medicine".

On October 19, 2018 Laekna Therapeutics reported that its Investigational New Drug (IND) application for LAE001 was officially accepted by Center for Drug Evaluation (CDE), China Food and Drug Administration (Press release, Laekna Therapeutics, OCT 19, 2018, View Source;article_id=42 [SID1234530434]).

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!

LAE001 is a novel, non-steroid, potent reversible dual inhibitor of Cytochrome P450 (CYP) 17A1 and CYP11B2. It will be mainly used as the treatment for metastatic prostate cancer.

Prostate cancer is one of the most common malignancies in men, and it is the second most common cause of cancer-related mortality (after lung cancer). In China, prostate cancer is the only one among the top ten cancers with yearly increased both the incidence rate and mortality rate. In most European and north America countries, the metastasis prostate cancer accounts only 15% of all prostate cancer. However, more than 50% of Chinese patients with prostate cancer had metastasis status at the time of diagnosis. Comparing to the current treatments for prostate cancer, LAE001 has demonstrated robust therapeutic efficacy and better safety profile in US phase I clinical trial. Due to its dual mechanism of inhibition of two critical enzymes for testosterone and aldosterone synthesis, LAE001 does not affect the levels of mineralocorticoid in men, and therefore reduces the risk of hyperaldosteronism and hepatotoxicity. LAE001 can also be used as a monotherapy without prednisone. It is expected that LAE001 will provide a better treatment option for the patients with prostate cancer after it is launched.

On October 19, 2018 TP Therapeutics, a clinical-stage precision oncology company developing novel drugs that address treatment resistance, reported its completion of an $80 million round of mezzanine financing (Press release, TP Therapeutics, OCT 19, 2018, View Source [SID1234530140]). Foresite Capital and venBio Partners led the investment syndicate, with participation from new investors HBM Healthcare Investments (Cayman) Ltd. and Nextech Invest. Also participating were existing investors including Cormorant Asset Management, Lilly Asia Ventures (LAV), Orbimed Advisors and SR One.

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!

TP Therapeutics will use the proceeds to advance its lead product candidate, Repotrectinib (TPX-0005), into a Phase 2 potential registration study in early 2019 for ROS1-positive non-small cell lung cancer (NSCLC) and NTRK-positive solid tumors. The study will enroll patients who already have received a tyrosine kinase inhibitor (TKI) and have developed resistance or were refractory, as well as those who are TKI treatment-naïve. TP Therapeutics will also use a portion of the funds to further develop its internally discovered pipeline.

In conjunction with the financing, TP Therapeutics announced that Athena Countouriotis, M.D., has been promoted to chief executive officer from her previous role of chief medical officer. Dr. Countouriotis also has been named to the board of directors. Co-founder Peter Li, Ph.D., M.B.A., who has served as chairman and CEO since the company was founded, has transitioned into a new role as head of TP Therapeutics Asia. In this role, he will focus on building relationships with clinical investigators and partners to expand the potential for TP Therapeutics’ pipeline in this important global region. Jean Cui, Ph.D., co-founder, president and chief scientific officer, has assumed the role of chairman. In addition, the board has added two new directors: Brett Zbar, M.D., managing director at Foresite Capital, and Robert Adelman, M.D., managing partner of venBio Partners.

"Our team has made tremendous achievements in the discovery and development of truly novel medicines targeting oncogenic drivers in the five years since Jean and I founded TP Therapeutics," said Dr. Li. "As we prepare for registration studies and move toward expanding our clinical pipeline, Athena is the right choice to lead our next chapter of growth. Her operational leadership and drug development experience are highly complementary with Jean and have shown to resonate both with our employees and investors."

Dr. Countouriotis joined TP Therapeutics in May 2018 as chief medical officer and executive vice president. Athena has broad oncology biotech leadership experience guiding multiple development programs through to market approval. She previously served as senior vice president and chief medical officer at Adverum Biotechnologies, and prior to that served in the same role at Halozyme Therapeutics. Additionally, she served as chief medical officer at Ambit Biosciences, leading the development of Quizartinib through the company’s initial public offering and acquisition by Daiichi Sankyo. Dr. Countouriotis also worked at Pfizer and Bristol-Myers Squibb in various clinical development roles for Sutent, Mylotarg, Bosulif, and Sprycel.

"I am honored to have the trust of our founders and our board as TP Therapeutics moves even closer to the patients it seeks to serve," said Dr. Countouriotis. "With the completion of the mezzanine financing, we are well funded to execute on our clinical and preclinical programs. I am pleased we have attracted this top-tier syndicate of investors."

Dr. Zbar commented: "TP Therapeutics has made great progress in the development of Repotrectinib, evidenced by the highly encouraging interim Phase 1 data presented recently at the World Conference on Lung Cancer. Targeted oncology is an area of focus for us, and the Foresite Capital team welcomes the opportunity to work closely with Athena again in her expanded leadership role."

Dr. Adelman added: "From the early discovery research to Phase 1 clinical development, the team at TP Therapeutics has been thoughtful in its approach to develop a truly differentiated therapy with potential to address some of the most difficult kinase fusions and their mutations. We look forward to working with Athena and the management team to advance Repotrectinib into the Phase 2 clinical study and ultimately build on its early success with the other novel assets in TP Therapeutics’ pipeline."

On October 19, 2018 Incyte (NASDAQ:INCY) reported Phase 2 preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Incyte, OCT 19, 2018, View Source [SID1234530093]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0 percent (95% CI: 50.6-87.9) in treatment-naive patients and 39.1 percent (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed.

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!

Results of the Novartis-sponsored Phase 2 study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (October 19, 2018 at 4:45 p.m. CEST / 10:45 a.m. EDT, Abstract LBA52).1

"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, M.D., University Hospital Cologne, Germany.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year.2 Approximately 3-4 percent of all patients with NSCLC have an identified MET mutation.3 Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation.4

"We are very pleased to announce these promising, preliminary results for capmatinib, another investigational medicine invented at Incyte that has the potential to be the first MET-selective targeted agent approved by the FDA," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We are encouraged by the results of this study and the potential for capmatinib to help patients with advanced MET mutated NSCLC, who face a poor prognosis and represent a clear unmet medical need."

About GEOMETRY mono-1

The GEOMETRY mono-1 trial is a multicenter, open-label, Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0 percent (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1 percent (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response.1,6

The most common treatment-related AEs included peripheral edema, nausea, vomiting and increased blood creatinine levels. Of patients treated with capmatinib, 83.8 percent experienced an AE, with 33.1 percent having grade 3/4 AEs.1,6

About Capmatinib

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor invented at Incyte that was licensed to Novartis in 2009. Under the Agreement, Incyte granted Novartis exclusive development and commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications. Novartis has stated that it expects to submit a new drug application to the U.S. Food and Drug Administration for capmatinib as a treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring MET amplification and/or mutations in 2019. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 percent and 14 percent on global sales by Novartis.