On March 11, 2025 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported positive topline results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer whose disease progressed following prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy (Press release, Arvinas, MAR 11, 2025, View Source [SID1234651065]). These are the first pivotal data for vepdegestrant, a potential first-in-class investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader.

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The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population.

"The first Phase 3 data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "We want to thank the patients and investigators who participated in this trial, and we look forward to sharing these data with health authorities as well as at a medical conference in 2025."

Overall survival was not mature at the time of the analysis, with less than a quarter of the required number of events having occurred. The trial will continue to assess overall survival as a key secondary endpoint. In the trial, vepdegestrant was generally well tolerated and its safety profile was consistent with what has been observed in previous studies. Detailed results from VERITAC-2 will be submitted for presentation at a medical meeting later this year, and these data will be shared with global regulatory authorities to potentially support regulatory filings.

"Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies," said Megan O’Meara, M.D., Interim Chief Development Officer, Pfizer Oncology. "These data from VERITAC-2 support the potential of vepdegestrant to give patients whose tumors harbor ESR1 mutations additional time without disease progression, compared to fulvestrant."

Vepdegestrant is an investigational oral PROTAC ER degrader for ER+/HER2- breast cancer being jointly developed by Arvinas and Pfizer and is designed to harness the body’s natural protein disposal system to specifically target and degrade the ER. In February 2024, the companies announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

About Metastatic Breast Cancer
About 2.3 million new breast cancer diagnoses were reported globally in 2022,1 and it is estimated there will be nearly 320,000 people diagnosed with breast cancer in the U.S. in 2025.2 Estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer accounts for approximately 70% of all cases.3

Nearly 30% of women initially diagnosed with early-stage breast cancer will ultimately develop metastatic breast cancer (MBC),4 the most advanced stage in which the disease has spread beyond the breast to other parts of the body. Treatment advances have helped those with MBC better manage symptoms, slow tumor growth, and may allow them to live longer, but most patients ultimately develop resistance to current standard-of-care treatments in the first-line setting and experience disease progression. ESR1 mutations are a common cause of acquired resistance and are found in approximately 40% of patients in the second-line setting.5 6 7

About the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global randomized study evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The trial enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.

Patients were randomized to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. The primary endpoint was progression-free survival (PFS) in the intent-to-treat and ESR1m populations as determined by blinded independent central review. Overall survival is a key secondary endpoint.

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC (PROteolysis TArgeting Chimera) protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER-positive (ER+)/human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

On March 11, 2025 Luminary Therapeutics reported that it has been awarded up to $5.8 million in funding from the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, to develop a mesothelin chimeric antigen receptor T cells ("CAR T") targeting non-small cell lung cancer and colorectal cancer (Press release, Luminary Therapeutics, MAR 11, 2025, View Source [SID1234651084]).

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"While CAR T therapies have been effective for blood cancers, solid tumors like lung and colorectal cancers have proven to be resistant to current CAR T therapies", said Jeff Liter, CEO and President of Luminary Therapeutics. "This project combines an allogeneic CAR T for direct killing of tumor cells with the ability to utilize the patient’s immune system to target tumor cells by also leveraging the gamma delta cell’s ability to work as professional antigen-presenting cells (APCs) and presenting tumor-specific neo antigens. Combining neo antigen-presenting functions with CAR directed killing in a single cellular chassis will increase the effectiveness of cellular therapies by recruiting a patient’s immune system to increase the response and durability of tumor clearance."

Since its founding in 2019, Luminary Therapeutics has developed a proprietary gamma delta expansion platform that is unique in the industry and allows Luminary to manufacture cell therapies with a significantly lower cost and reduced time to clinic. Leveraging this platform, the Company has developed two groundbreaking therapeutic programs designed to overcome current challenges of CAR T therapies for solid tumors and autoimmune disorders. The award from ARPA-H represents not only a significant step forward in scaling Luminary’s therapeutic pipeline, while expanding the capabilities of its gamma delta expansion platform, but also aligns with ARPA-H’s mission to improve health outcomes for everyone.

On March 11, 2025 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that members of its management team will present an overview of the company at the upcoming 37th Annual Roth Conference (Press release, Cellectar Biosciences, MAR 11, 2025, View Source [SID1234651066]). Details are as follows:

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Date: Monday, March 17
Time: 8:30 AM Eastern Time
Webcast: Click HERE

A replay of the corporate presentation will be available on the Events section of the company’s Investor Relations website.

On March 11, 2025 Artera, the developer of multimodal artificial intelligence (MMAI)-based prognostic and predictive cancer tests, reported the first patient enrollment in PROSTATE-IQ, a Phase 3 clinical trial in men with prostate cancer recurrence after prostatectomy (Press release, Artera, MAR 11, 2025, View Source [SID1234651085]). The trial utilizes the ArteraAI Prostate Test to enable treatment personalization by determining cancer metastasis risk and identifying whether patients may be able to reduce or avoid hormone therapy.

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The trial is being led by Karen Elizabeth Hoffman, M.D., Professor of Radiation Oncology, and Mays Radiation Oncology Center Medical Director at The University of Texas MD Anderson Cancer Center.

"We are excited to partner with some of the world’s leading institutions on this transformational clinical trial, one that can radically improve not only patient outcomes but the quality of life for men with prostate cancer," said Tim Showalter, M.D., Chief Medical Officer of Artera. "There has been tremendous eagerness from the medical community to start adopting risk stratification tools in this fashion with this patient population – those with biochemical recurrence after prostatectomy. We’re excited to see our test being used to help determine the optimal treatment therapy, reduce unnecessary side effects, and increase confidence in treatment planning."

The current standard of care for these patients is radiation, oftentimes combined with a hormone therapy called androgen deprivation therapy (ADT). ADT is often successful in improving outcomes, but it also causes many difficult side effects including fatigue, sexual dysfunction, hot flashes, cognitive changes, metabolic dysregulation, and weight gain, negatively impacting men’s quality of life.

Using the ArteraAI Prostate Test on post-prostatectomy surgical specimens, patients in the trial will be risk-stratified into two groups: 1) low-risk patients who will be randomized to either 6 months of ADT or apalutamide monotherapy, which avoids the difficult side effects of testosterone suppression, thereby preserving their quality of life, and 2) high-risk patients who will be randomized to either 24 months of ADT or 6 months of ADT with apalutamide.

The trial’s primary endpoint will assess the patients’ general quality of life, using questionnaires and wearable devices. Secondary endpoints will include physician-reported toxicity, patient-reported activity, sleep, cognitive function, mental health, body composition changes, and cancer control metrics.

The primary site for the trial is MD Anderson Cancer Center, with up to 10 additional sites including Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, and OhioHealth. The trial is actively enrolling patients across sites.

To learn more or to enroll in the trial, visit: View Source

On March 11, 2025 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported that the European Commission (EC) has granted marketing authorization for RYTELO (imetelstat) as a monotherapy for the treatment of adult patients with transfusion-dependent (TD) anemia due to very low, low or intermediate risk myelodysplastic syndromes (lower-risk MDS or LR-MDS) without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy (ESAs) (Press release, Geron, MAR 11, 2025, View Source [SID1234651067]). Lower-risk MDS is a progressive blood cancer with high unmet need, where many patients with anemia become dependent on red blood cell transfusions, which can be associated with clinical consequences and decreased quality of life.

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"As the first and only treatment of its kind, RYTELO represents an important new option – significantly reducing the need for red blood cell transfusions for people living with LR-MDS who are battling debilitating symptoms like anemia and fatigue," said Joseph Eid, M.D., Geron’s Executive Vice President, Research and Development. "This approval from the European Commission, just nine months following approval in the U.S., underscores the positive benefit for these patients demonstrated in our clinical trials and we look forward to making this innovative therapy accessible to eligible patients in Europe."

"I am thrilled that the European Commission has approved RYTELO in LR-MDS. The long-term and durable responses observed in the Phase 3 IMerge study reinforce the practice-changing potential of telomerase inhibition as a clinically meaningful and differentiated option for the treatment of lower-risk MDS," said Uwe Platzbecker, M.D., Chief Medical Officer at the University Hospital Carl Gustav Carus Dresden in Germany, who was an IMerge investigator and a co-lead author of the Phase 3 results published in The Lancet . "Physicians and patients in Europe are now one step closer to accessing a novel treatment that, in addition to having a generally manageable safety profile, has the potential to provide extended and continuous red blood cell transfusion independence."

The marketing authorization of RYTELO approved by the EC is supported by data from the IMerge Phase 3 clinical trial, which demonstrated the significant clinical benefit of RYTELO in patients with transfusion-dependent anemia due to LR-MDS, reducing the need for red blood cell transfusions in the first 24 weeks of treatment compared to placebo, as observed in the double-blind controlled study. The safety profile of RYTELO was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most commonly reported adverse reactions ≥ Grade 3 were neutropenia (69%), thrombocytopenia (63%), which lasted a median duration of less than two weeks, and in more than 80% of patients were resolved to Grade < 2 in under four weeks.

RYTELO is the first and only telomerase inhibitor approved by the EC, and the marketing authorization applies to all 27 European Union member states, and Iceland, Norway and Liechtenstein. Geron is preparing to commercialize RYTELO in select EU countries beginning in 2026, pending country-by-country reimbursement. Additionally, Geron is exploring opportunities to make RYTELO available to eligible patients through Expanded Access Programs (EAP), including Named Patient Programs (NPP), which are designed to support access for individual patients on a case-by-case basis.

In connection with the approval, the EMA’s Committee of Orphan Medicinal Products (COMP) reviewed and issued a positive opinion to maintain RYTELO’s orphan drug designation in the EU for MDS, which is expected to provide market exclusivity for ten years after approval, subject to maintaining orphan designation. Patent exclusivity in the EU for LR-MDS is anticipated into 2038, subject to approval of patent term extension by the European Patent Office.

About Lower-Risk Myelodysplastic Syndromes (LR-MDS)

Lower-risk myelodysplastic syndromes (LR-MDS) is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue1 . These symptomatic LR-MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short- and long-term clinical consequences that reduce quality of life and shorten survival2,3 . There is a high unmet need for many LR-MDS patients, particularly those with characteristics having poorer prognosis. Current treatment options for those failing ESA are limited to select sub-populations and there is an unmet need for treatments that can provide extended and continuous red blood cell transfusion independence.

About RYTELO (imetelstat)

RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration and the European Commission.

U.S. IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.

Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.

Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).

Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Please see RYTELO (imetelstat) full Prescribing Information, available at View Source

The Summary of Product Characteristics (SmPC) for RYTELO in the EU is available at View Source