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SpringWorks Therapeutics Receives Positive CHMP Opinion for Nirogacestat for the Treatment of Adults with Desmoid Tumors

On June 20, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of nirogacestat, an oral gamma secretase inhibitor, as monotherapy for the treatment of adults with progressing desmoid tumors who require systemic treatment (Press release, SpringWorks Therapeutics, JUN 20, 2025, View Source [SID1234654023]). The European Commission (EC) will review the CHMP opinion and is expected to make a final decision regarding the approval in the third quarter of 2025.

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"The positive opinion from the CHMP reflects the meaningful benefits nirogacestat can offer patients in Europe where currently there are no approved treatment options," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to the European Commission’s decision as we strive to bring nirogacestat to desmoid tumor patients globally."

Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. The CHMP opinion was based on the Marketing Authorization Application (MAA) for nirogacestat, which centered on results from the Phase 3 DeFi trial that were published in The New England Journal of Medicine.1 In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a 71% lower risk of disease progression compared to placebo. Nirogacestat demonstrated a significant improvement in objective response rate as well as early and sustained improvements in patient-reported outcomes (PROs), including pain, physical functioning and overall quality of life.

Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse reactions reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

"Desmoid tumors can have a profound impact on patients as well as their loved ones, and the positive CHMP opinion underscores the potential benefit of nirogacestat for these patients," Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial. "It is very encouraging that a significant number of people taking nirogacestat experienced reductions in their tumor size and also rapid and sustained relief of their desmoid tumor symptoms, including pain."

Nirogacestat is approved in the U.S. for the treatment of adults with progressing desmoid tumors who require systemic treatment.

About the DeFi Trial
DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi also included an open-label extension phase.

About Desmoid Tumors
Desmoid tumors are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.2,3

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.4,5 It is estimated that there are 1,300-2,300 new desmoid tumor cases diagnosed per year in the European Union.6,7

Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.5,8 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.9,10

About Nirogacestat

Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority.

Ratio Therapeutics and TerraPower Isotopes Sign Supply Agreement for Actinium-225 For Targeted Radiotherapeutics

On June 20, 2025 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, and TerraPower Isotopes, a subsidiary of TerraPower, a leading nuclear innovation company, reported they entered into a supply agreement for the medical radioisotope actinium-225 (Ac-225) (Press release, Ratio Therapeutics, JUN 20, 2025, View Source [SID1234654022]). Under the agreement, TerraPower Isotopes would supply Ratio with quantities of non-cGMP Ac-225 for use to incorporate into or use in the development of Ratio’s radiopharmaceuticals.

Ac-225 plays a vital role in the development of next-generation radiopharmaceuticals, serving as a powerful alpha-emitting isotope used in targeted cancer therapies. For Ratio, access to a reliable supply of Ac-225 is essential to advancing its pipeline based on its proprietary Trillium and Macropa platforms. Together, these platforms enable the design and development of novel radiopharmaceuticals that can selectively target and eradicate cancer cells, offering a powerful and targeted approach to cancer treatment.

"Securing a reliable supply of Actinium-225 is a critical step in advancing our pipeline of targeted alpha therapies," said John Babich, Ph.D., President and Chief Scientific Officer of Ratio. "This agreement with TerraPower Isotopes strengthens our ability to scale production and advance our Trillium and Macropa platforms, which are purpose-built to fully harness the therapeutic potential of Actinium-225 in targeted alpha therapies."

"TerraPower Isotopes is committed to increasing the global supply of Actinium-225 to support cancer treatment research and development," said Scott Claunch, President of TerraPower Isotopes. "We’re proud to work with Ratio Therapeutics to help realize the full potential of Actinium-225 in radiopharmaceuticals. Once linked to a disease-targeting molecule, Actinium-225 labeled drug products can be precisely delivered to cancerous tissues, where they emit high-energy alpha particles capable of destroying tumor cells while sparing surrounding healthy tissue, making it a potentially transformative treatment option for patients."

Ratio Therapeutics and TerraPower Isotopes Sign Supply Agreement for Actinium-225 For Targeted Radiotherapeutics

Moleculin Announces $5.9 Million Public Offering

On June 20, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported the pricing of a public offering consisting of 16,080,000 shares of common stock (or pre-funded warrants in lieu thereof) and Series E warrants to purchase up to 48,240,000 shares of its common stock, at a combined public offering price per share of common stock (or per pre-funded warrant in lieu thereof) and accompanying Series E warrants of $0.37 (Press release, Moleculin, JUN 20, 2025, View Source [SID1234654021]). The Series E warrants will have an exercise price of $0.37 per share, are exercisable upon stockholder approval, and will expire five years following the initial exercise date.

The offering is expected to close on or about June 23, 2025, subject to customary closing conditions. Gross proceeds, before deducting placement agent fees and commissions and offering expenses, are expected to be approximately $5.9 million. The Company intends to use the net proceeds from the offering to advance Annamycin and its other two drug portfolios through clinical development, advancing the remainder of the existing portfolio through preclinical studies and into INDs or their equivalent, sponsoring research, and for working capital.

Roth Capital Partners is acting as exclusive placement agent of the offering. Maxim Group LLC is acting as financial advisor to the Company.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-287727), that was declared effective by the U.S. Securities and Exchange Commission ("SEC"), on June 20, 2025. The offering is being made only by means of a prospectus forming part of the effective registration statement relating to the offering. A preliminary prospectus relating to the offering has been filed with the SEC. Electronic copies of the final prospectus relating to and describing the terms of the offering may be obtained, when available, at the SEC’s website at www.sec.gov or by contacting Roth Capital Partners, LLC, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660 or by email at [email protected].

This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

Ipsen receives positive CHMP opinion for Cabometyx® in previously treated advanced neuroendocrine tumors

On June 20, 2025 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for Cabometyx (cabozantinib) for adult patients with unresectable or metastatic, well differentiated extra-pancreatic (epNET) and pancreatic (pNET) neuroendocrine tumors who have progressed following at least one prior systemic therapy other than somatostatin analogues (Press release, Ipsen, JUN 20, 2025, View Source [SID1234654020]). This recommendation is based on results from the CABINET Phase III trial presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 and published in the New England Journal of Medicine.3,4 A final decision on the approval in the European Union is expected in the coming months.

The number of people newly diagnosed with neuroendocrine tumors (NETs) is believed to be increasing, with a higher estimated prevalence than pancreatic or bladder cancer.5,6,7 Most forms of NETs develop slowly and can originate in various parts of the body,8 often requiring multiple lines of therapy as the disease progresses.1,2 Treatment options upon progression are often limited depending on primary tumor site and other factors, making it challenging to define optimal sequencing of treatments specific to individual patient needs.1,2,9 In particular, for the 27% of people diagnosed with lung NETs,10 there are no approved treatment options available upon progression on a non-somatostatin analogue-based systemic therapy.1,2

"The significant efficacy data demonstrated in the CABINET Phase III trial have provided the opportunity to reframe conversations on care approaches for people living with advanced pancreatic and extra-pancreatic neuroendocrine tumors," said Christelle Huguet, PhD, EVP and Head of Research and Development, Ipsen. "Today’s positive CHMP opinion confirms the potential to translate these data into meaningful benefits for patients and we look forward to receiving the final decision from the European Commission."

The five-year survival rate is highly dependent on the primary site of disease. For advanced gastrointestinal and lung NETs, where the cancer has spread to distant parts of the body, the five-year survival rates are 68% and 55%, respectively.11,12 For people diagnosed with advanced pNET, however, the prognosis is poor, with a five-year survival rate of 23%.13

The positive CHMP opinion is based on data from the CABINET Phase III trial, which investigated Cabometyx versus placebo in people living with advanced pNETs or epNETs, whose disease had progressed after prior systemic therapy other than somatostatin analogues.3,4

In the pNET cohort, at a median follow-up of 13.8 months, median PFS was 13.8 months for Cabometyx versus 4.4 months for placebo (hazard ratio (HR) 0.23 [95% confidence interval (CI) 0.12-0.42] p<0.001).3,4
In the epNET cohort, at a median follow-up of 10.2 months, median PFS based on local radiology review was 8.4 months for Cabometyx versus 3.9 months for placebo (HR 0.38 [95% CI 0.25-0.59] p<0.001).3,4
Overall survival data were not mature at the time of the analyses and potentially confounded by the crossover design of the CABINET trial.3,4
The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were identified.3,4
Per presentation at the Annual Society of Clinical Oncology Annual Meeting 2025, health-related quality of life was also found to be maintained or improved.14
About Cabometyx

Cabometyx is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).15 These receptor tyrosine kinases are involved in both normal cellular function and pathological processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, immune modulation, and maintenance of the tumor microenvironment.15,16,17,18

Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S.

In over 65 countries outside of the United States and Japan, including in the European Union, Cabometyx is currently indicated as:16

Monotherapy for advanced renal cell carcinoma (aRCC).
as first-line treatment of adults with intermediate- or poor-risk disease.
in adults following prior VEGFR-targeted therapy.
A combination with nivolumab for the first-line treatment of aRCC in adults.
Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy.
Monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib.
About CABINET (Alliance A021602)

CABINET (randomized, double-blinded Phase III trial of CABozantinib versus placebo In patients with advanced NEuroendocrine Tumors after progression on prior therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health in the U.S., and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network, as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

The multicenter, Phase III CABINET pivotal trial enrolled a total of 298 patients in the U.S. at the time of the analysis. Patients were randomized 2:1 to Cabometyx or placebo in two separately powered cohorts. The epNET cohort included patients with the following primary tumor sites: gastrointestinal tract, lung, unknown primary and other organs. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. Food and Drug Administration-approved line of prior systemic therapy other than somatostatin analogues. The primary endpoint in each cohort was PFS per RECIST 1.1 by retrospective independent central review. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with Cabometyx. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.