On June 3, 2022 Taiho Oncology, Inc. reorted updated results of the Phase 2 FOENIX-CCA2 trial of futibatinib, confirming results observed in an earlier analysis (Press release, Taiho, JUN 3, 2022, View Source [SID1234615547]). The trial was conducted in patients with locally advanced or metastatic unresectable intrahepatic (inside the liver) cholangiocarcinoma (iCCA) harboring FGFR2 gene rearrangements including fusions . These data were presented as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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"Updated data from the pivotal FOENIX-CCA2 Phase 2 trial reinforce the durable efficacy and continued tolerability of futibatinib in previously treated patients with locally advanced or metastatic iCCA harboring FGFR2 gene rearrangements including fusions," said medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center in Boston, and lead investigator on the study. "These data add to the body of evidence supporting futibatinib as a potential treatment option for patients living with this rare cancer that traditionally has had limited treatment options."

Each year, approximately 8,000 individuals in the U.S. are diagnosed with cholangiocarcinoma (CCA),1 a cancer of the bile ducts of the liver. Worldwide, approximately 0.3-6 people per 100,000 individuals live with CCA.2 CCA is mainly seen in people 65 years of age or older,3 and treatment options are limited. FGFR2 gene rearrangements, including gene fusions, which can form a hybrid gene and promote tumor proliferation, are observed more frequently in the iCCA patient population, with approximately 10-16% of patients having tumors with these rearrangements.4,5,6,7,8

The Phase 2 FOENIX-CCA2 trial included 103 patients with locally advanced or metastatic unresectable iCCA harboring FGFR2 gene rearrangements including fusions who had received one or more prior lines of systemic therapy. Patients received futibatinib 20 mg once daily until disease progression or unacceptable toxicity. The primary endpoint of the trial was objective response rate (ORR) as assessed by independent central review.

At the time of the data cutoff for this updated analysis, with a median follow-up of 25.0 months, the ORR was 41.7%. Responses were durable, with a median duration of response (DoR) of 9.5 months (74% of responses lasted greater than six months). In addition, the disease control rate was 82.5%, median progression-free survival was 8.9 months and median overall survival was 20.0 months.

The most common treatment-related adverse events (TRAEs) were hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%) and fatigue (25%). Most TRAEs were of mild or moderate intensity and manageable. There were two patients with grade 4 TRAEs and four patients discontinued treatment due to TRAEs. No treatment-related deaths occurred.

"Taiho Oncology remains committed to addressing unmet treatment needs in patients living with a broad range of cancers, and these data from the FOENIX-CCA2 trial demonstrate the clinical activity of futibatinib," said Volker Wacheck, Vice President, Clinical Development, Taiho Oncology, Inc. "We are looking forward to continued discussions with regulatory authorities around this important investigational therapy."

In March 2022, the U.S. Food and Drug Administration (FDA) accepted for priority review the New Drug Application (NDA) for futibatinib in the treatment of patients with previously treated locally advanced or metastatic CCA harboring FGFR2 gene rearrangements, including gene fusions. The FDA provided an anticipated Prescription Drug User Fee Act (PDUFA) action date of September 30, 2022. The FDA previously granted Breakthrough Therapy Designation (BTD) for futibatinib in CCA in February 2021.

About Futibatinib
Futibatinib (TAS-120) is an investigational, oral, potent, selective and irreversible tyrosine kinase inhibitor of FGFR1, 2, 3 and 4. This irreversible binding to the ATP binding pocket of FGFR1-4 results in the inhibition of FGFR-mediated signal transduction pathways, reduced tumor cell proliferation and increased cell death in tumors with FGFR1-4 genetic aberrations. Futibatinib is being studied alone as a potential treatment for patients with advanced solid tumors with FGFR1-4 genomic aberrations, including cholangiocarcinoma, or in combination with chemotherapy or other therapies.

On June 3, 2022 Novartis reported results of an exploratory retrospective biomarker analysis finding that different genetic mutation profiles in tumors harboring PIK3CA mutation did not affect treatment benefit with Piqray (alpelisib) plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer following progression on or after an endocrine-based regimen (Press release, Novartis, JUN 3, 2022, View Source [SID1234634694]). Selected as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1006), the retrospective analysis of data from the Phase III SOLAR-1 study found that the clinical benefit of the Piqray and fulvestrant combination was maintained regardless of genetic alterations in most biomarkers, including ESR1 and genes implicated in resistance to CDK4/6 inhibitors1.

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"This analysis evaluating alpelisib and fulvestrant across HR+/HER2- advanced breast cancer tumors with different genetic alterations confirms the importance of using alpelisib to selectively target PIK3CA as a major oncogenic driver in these tumors," said Dejan Juric, MD, Director, Termeer Center for Target Therapies, Mass General Cancer Center in Boston.

"PIK3CA mutations affect approximately 40% of those with the HR+/HER2- subtype and are known oncogenic drivers of metastatic breast cancer, associated with endocrine resistance and an overall worse prognosis—so it’s critical for physicians to test and treat with Piqray for patients with PIK3CA mutations upfront consistent with ASCO (Free ASCO Whitepaper) and NCCN guidelines," said Reshema Kemps-Polanco, Executive Vice President, US Oncology at Novartis.

Highlights from the SOLAR-1 biomarker retrospective analysis at ASCO (Free ASCO Whitepaper)

Patients with ESR1 gene alterations achieved 12.0 months of median progression-free survival (mPFS) when treated with Piqray and fulvestrant compared to 6.5 months for those treated with fulvestrant alone1.
Even patients with FGFR1 and FGFR2 gene alterations, which have been associated with resistance to CDK4/6 inhibitors, had benefit when treated with Piqray plus fulvestrant (12.7 months and 9.6 months mPFS, respectively), compared to those treated with fulvestrant alone (3.8 months and 2.8 months mPFS, respectively)1.
The benefit seen with the Piqray and fulvestrant combination was independent of additional genetic alterations, including TP53, CCND1, MAP3K1 and ARID1A; genes in the MAPK pathway, genes implicated in CDK4/6 inhibitor resistance such as RB11.
Real-world evidence supports effectiveness of Piqray in tumors with PIK3CA mutation
A real-world retrospective analysis (Abstract #1055) showed clinical benefit for 157 patients with HR+/HER2- advanced or metastatic breast cancer with PIK3CA genetic mutation following treatment with Piqray plus fulvestrant, even when exposed to prior treatment with fulvestrant, confirming the oncogenic dependence of the tumor on the PIK3CA mutation2. In the analysis, prior fulvestrant treatment included CDK4/6 inhibior plus fulvestrant (74.5%), fulvestrant alone (33.8%), and non-CDK4/6 inhibitor plus fulvestrant (21.0%)2.

About PIK3CA-mutated Breast Cancer
An estimated 361,826 people are diagnosed with metastatic breast cancer worldwide each year, and approximately 40% of those with HR+/HER2- subtype have tumors that harbor a PIK3CA mutation, which is associated with a poor prognosis6-7.

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen3. Piqray is approved in over 70 countries, including the US6. In the European member states, Piqray plus fulvestrant is approved after disease progression following endocrine therapy as monotherapy8.

Novartis is continuing to reimagine cancer with additional trials of Piqray. To complement the SOLAR-1 study, EPIK-B5, a large Phase III clinical trial is conducted with Piqray in combination with fulvestrant following treatment with a CDK4/6 inhibitor and aromatase inhibitor9. Novartis is also studying the potential of Piqray in triple-negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical trial, in advanced HER2+ breast cancer in the EPIK-B2 Phase III clinical trial and in ovarian cancer in the EPIK-O Phase III clinical trial10-12.

On June 3, 2022 Bristol Myers Squibb (NYSE:BMY) and Turning Point Therapeutics, Inc. (NASDAQ:TPTX) reported a definitive merger agreement under which Bristol Myers Squibb will acquire Turning Point Therapeutics for $76.00 per share (Press release, Turning Point Therapeutics, JUN 3, 2022, View Source [SID1234615500]). The transaction was unanimously approved by both the Bristol Myers Squibb and Turning Point Therapeutics Boards of Directors and is anticipated to close during the third quarter of 2022.

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Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of investigational medicines designed to target the most common mutations associated with oncogenesis. Turning Point Therapeutics’ lead asset, repotrectinib, is a next-generation, potential best-in-class tyrosine kinase inhibitor (TKI) targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors. Repotrectinib has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration. In the Phase 1/2 TRIDENT-1 clinical trial, longer duration of response has been observed in the landmark analysis with repotrectinib than with existing ROS1 agents in first-line NSCLC.

Bristol Myers Squibb expects repotrectinib to be approved in the U.S. in the second half of 2023 and become a new standard of care for patients with ROS1-positive NSCLC in the first-line setting. The company also plans to continue to explore the potential of Turning Point Therapeutics’ promising pipeline of novel compounds.

"The acquisition of Turning Point Therapeutics further broadens our leading oncology franchise by adding a best-in-class, late-stage precision oncology asset," said Giovanni Caforio, M.D., Board Chair and Chief Executive Officer, Bristol Myers Squibb. "With this transaction, we are continuing our strong track record of strategic business development to further enhance our growth profile."

"Today’s news builds upon our long legacy of pioneering next-generation medicines for patients with cancer," said Samit Hirawat, M.D., Chief Medical Officer, Global Drug Development, Bristol Myers Squibb. "With repotrectinib, we have the opportunity to change the standard of care and address a significant unmet medical need for ROS1-positive non-small cell lung cancer patients."

"Through this transaction, we will be able to harness the full potential of our precision oncology platform to advance the standard of care for cancer patients. Since our founding, we have leveraged our deep scientific expertise to develop a pipeline of promising precision oncology assets," said Athena Countouriotis, M.D., President and Chief Executive Officer, Turning Point Therapeutics. "With Bristol Myers Squibb’s leadership in oncology, strong commercial capabilities and manufacturing footprint, we will be able to further accelerate the pace at which we can bring our novel medicines to benefit people diagnosed with cancer around the world."

Financial Details and 2022 Financial Guidance

The transaction supports Bristol Myers Squibb’s medium- to long-term growth strategy with accretion to non-GAAP earnings per share (EPS) beginning in 2025. The transaction is expected to be up to $0.08 per share dilutive to non-GAAP EPS in 2022 prior to any impact from an acquired in-process research and development charge based on final accounting treatment. The accounting treatment as a business combination or asset acquisition will be determined upon the expected close of the transaction in the third quarter of 2022.

Transaction Terms and Financing

Under the terms of the merger agreement, Bristol Myers Squibb will promptly commence a tender offer to acquire all of the outstanding shares of Turning Point Therapeutics’ common stock at a price of $76.00 per share in an all-cash transaction for a total consideration of $4.1 billion in equity value. Turning Point Therapeutics’ Board of Directors unanimously recommends that Turning Point Therapeutics shareholders tender their shares in the tender offer.

The transaction is subject to customary closing conditions, including the tender of a majority of the outstanding shares of Turning Point Therapeutics’ common stock and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Following the successful closing of the tender offer, Bristol Myers Squibb will acquire all remaining shares of Turning Point Therapeutics that are not tendered into the tender offer through a second-step merger at the same price of $76.00 per share.

Bristol Myers Squibb expects to finance the acquisition with cash on hand.

Advisors

Gordon Dyal & Co., LLC is serving as the exclusive financial advisor to Bristol Myers Squibb, and Kirkland & Ellis LLP is serving as legal counsel. Goldman Sachs & Co. LLC is serving as the exclusive financial advisor to Turning Point Therapeutics, and Cooley LLP is serving as legal counsel.

On June 3, 2022 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported encouraging preliminary safety and efficacy results from its Phase 1B study of unesbulin (PTC596) in advanced leiomyosarcoma (LMS) patients (Press release, PTC Therapeutics, JUN 3, 2022, View Source [SID1234615516]). The results demonstrated that treated patients achieved an 18.2 percent objective response rate and a 51.5 percent disease control rate. In addition, unesbulin was generally well tolerated. The results from the dose escalation study which evaluated unesbulin in combination with dacarbazine (DTIC), will be presented on Saturday, June 4, during the Sarcoma Oral Abstract Session beginning at 1:15 p.m. CDT at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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"The results demonstrated with unesbulin in LMS patients are very promising," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics. "Leiomyosarcoma is an aggressive soft tissue sarcoma that has significant high unmet medical need, especially for those patients who have relapsed or are refractory to current treatments. We are excited to bring a new chemical entity to the fight against cancer."

The primary objectives of the study were to determine the recommended Phase 2 dose (RP2D) of unesbulin in combination with DTIC and to characterize the safety profile of the combination. In addition, the secondary objectives included progression free survival and duration of response. Unesbulin 300 mg taken twice a week in combination with DTIC 1,000 mg/m2 every 21 days was established as the RP2D.

"Leiomyosarcoma is a particularly aggressive tumor type that desperately requires new treatment options for patients," said Brian Van Tine, M.D., Ph.D., Sarcoma Program, Washington University and lead clinical investigator. "The preliminary results demonstrate promising early efficacy in patients with advanced leiomyosarcoma."

Based on the preliminary data from the Phase 1B study, PTC has initiated the SUNRISE LMS study. SUNRISE LMS is an international, placebo-controlled, registration-directed study comparing the efficacy and safety of unesbulin and DTIC versus placebo and DTIC in patients with advanced LMS who have received ≥1 prior line of systemic therapy. The study is ongoing (ClinicalTrials.gov identifier: NCT05269355).

About Unesbulin (PTC596)
Unesbulin is an investigational oral tubulin binding agent that arrests tumor cells in G2/M phase, including cancer stem cells, through the action of inhibiting tubulin polymerization. Unesbulin was discovered through PTC’s proprietary discovery platform.

About Leiomyosarcoma
Leiomyosarcoma (LMS) is a rare and aggressive cancer found in smooth muscle tissue. LMS is one of the more aggressive sarcoma subtypes representing 10 to 28 percent1 of all soft tissue sarcomas and has a high risk of recurrence leading to decreased disease-specific survival.2 Approximately 4,000 patients are diagnosed each year in the United States and there is a 2:1 incidence in females compared to males.3

On June 3, 2022 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on sickle cell disease, prostate cancer and other rare hematologic diseases and cancers, reported that it will participate in the Jefferies Healthcare Conference taking place June 8-10, 2022 (Press release, Forma Therapeutics, JUN 3, 2022, View Source [SID1234615532]). Forma will present on June 9, 2022 at 2:00 p.m. Eastern Daylight Time (EDT).

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A webcast of the conference presentation will be available in the "News & Investors" section of Forma’s website at www.FormaTherapeutics.com.