On September 18, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy in oncology, inflammation and immunology (I&I), reported the completion of the safety run-in and the determination of recommended Phase 2 dose (RP2D) for its ongoing Phase 1b/2 STARt-002 trial (Press release, Marengo Therapeutics, SEP 18, 2025, View Source [SID1234656077]). The study, evaluating Marengo’s dual T-cell agonist invikafusp alfa in combination with TRODELVY (sacituzumab govitecan-hziy), Gilead’s approved TROP2-directed antibody-drug conjugate (ADC), is now advancing into two expansion cohorts in HR+/HER2− and TNBC metastatic breast cancer, respectively.

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"Breast cancer remains an area of tremendous unmet need, particularly for patients with advanced HR+/HER2− and triple-negative disease," said Erika Hamilton, M.D. FASCO, Director of Breast Cancer Research at Sarah Cannon Research Institute (SCRI). "The ability to combine a novel T cell agonist like invikafusp with a proven ADC such as sacituzumab govitecan represents an exciting step toward potentially broadening the benefit of immunotherapy-based combination regimens for patients with historically limited treatment options. The enthusiasm we’re seeing among investigators and patients to participate in STARt-002 reflects the promise of this approach."

"As highlighted at recent oral presentations at major scientific conferences, invikafusp has already demonstrated promising single-agent activity in PD-1 resistant tumors including breast cancer," said Kevin Chin, M.D., Chief Medical Officer of Marengo Therapeutics. "Advancing STARt-002 into Phase 2 expansion cohorts reinforces invikafusp’s potential as an immunotherapy backbone, particularly in combination with ADCs for immunologically cold tumors such as breast cancer. We look forward to building on this momentum as we generate additional clinical data in both monotherapy and combination settings."

The STARt-002 study (NCT06827613) is currently enrolling patients across leading North American cancer centers including Massachusetts General Hospital, SCRI, Princess Margaret Cancer Centre, University of Southern California, University of California Los Angeles, University of Texas at San Antonio and Ohio State University, with participation from additional sites in the near term.

On September 18, 2025 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported that the company completed a Type A meeting with the U.S. Food and Drug Administration (FDA) on September 16th to discuss the complete response letter (CRL) for the Company’s Biologics License Application (BLA) for RP1 in combination with nivolumab for the treatment of advanced melanoma (Press release, Replimune, SEP 18, 2025, View Source [SID1234656074]).

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The company is evaluating the feedback from the FDA provided during the meeting to determine next steps. At this time, a path forward under the accelerated approval pathway has not been determined.

"The feedback from the melanoma community, including patients and physicians, clearly highlights the unmet need in advanced melanoma and the compelling risk-benefit profile of RP1 observed in the IGNYTE trial," said Sushil Patel, Ph.D., CEO of Replimune. "We remain committed to working with the FDA to determine an expeditious path forward for RP1."

About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

On September 18, 2025 PDS Biotechnology Corporation (Nasdaq: PDSB) ("PDS Biotech" or the "Company"), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers, reported details of a sub-analysis of the cohort of patients with low PD-L1 expression (CPS 1-19) from the final data for its recently completed VERSATILE-002 Phase 2 clinical trial (Press release, PDS Biotechnology, SEP 18, 2025, View Source [SID1234656073]). The VERSATILE-002 trial evaluated PDS0101 (Versamune HPV) + Keytruda in patients with HPV16-positive first-line recurrent and/or metastatic head and neck squamous cell cancer ("1L R/M HNSCC").

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"This is great news for these patients who may now have the possibility of a well-tolerated treatment without chemotherapy" stated Prof. Kevin Harrington, M.D., Head of the Division of Radiotherapy, The Institute of Cancer Research, London.

"Patients with low levels of PD-L1 expression have typically shown poor response to immune checkpoint inhibitor therapy, leaving HNSCC patients in this sub-type with few viable treatment options and a poor prognosis," said Kirk Shepard, M.D., Chief Medical Officer of PDS Biotech. "This sub-analysis of survival data from the CPS 1-19 patient cohort appears to show that the multifunctional T cell immune response of PDS0101 treatment may overcome the documented limitations of immune checkpoint inhibitor therapy and significantly improve survival in one of the most difficult-to-treat patient populations. This is a very encouraging finding, pointing to the potential of PDS0101 to improve treatment outcomes in a patient group that has historically derived limited benefit from current standards of care."

Approximately 60% of the patients enrolled (n=53) in the VERSATILE-002 trial had low PD-L1 expression, a difficult to treat subset of the overall HNSCC patient population. The sub-analysis of this patient cohort shows:
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Median overall survival (mOS) for patients within the CPS 1-19 cohort (n=32) was 29.5 months.
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Published mOS in this CPS cohort was 10.8 months with Keytruda monotherapy and 12.3 months with Keytruda plus chemotherapy*

The Company announced mOS results for the full study population of 39.3 months from the VERSATILE-002 trial on August 25, 2025, and the full data set for the trial is expected to be published later this year.

*No head-to-head studies have been performed comparing Keytruda (pembrolizumab) monotherapy and Keytruda plus chemotherapy with PDS0101 *

About the VERSATILE-002 Trial
VERSATILE-002 (NCT04260126) is an open-label, multi-center Phase 2 clinical trial evaluating the safety and efficacy of PDS0101, an HPV16-targeted immunotherapy, in combination with pembrolizumab for unresectable, recurrent or metastatic HPV16-positive HNSCC. The trial is designed to assess the combination therapy’s impact on patients who are either naive to or refractory to immune checkpoint inhibitors.

On September 18, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company focused on innovative cancer therapeutics, reported positive efficacy data from its ongoing Phase 2 clinical trial of ENV105 (carotuximab) in patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Kairos Pharma, SEP 18, 2025, View Source [SID1234656072]). Kairos Pharma is hosting a virtual KOL (key opinion leader) event to provide perspectives on this data at 5 p.m. ET / 2 p.m. PT today. Interested participants can sign-up to receive the webcast link here View Source

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All patients enrolled in the trial had already failed at least one other hormone therapy modality. This predetermined interim analysis covers the same 10 patients from the safety-arm of the trial, with all patients having failed at least one androgen receptor inhibitor hormone therapy prior to acceptance. Two of the ten patients withdrew from the trial for unrelated events. Of the eight remaining patients, the median progression-free survival was more than 13 months, with five of the eight patients continuing treatment without progression. Seven of nine patients demonstrated a decrease of their prostate-specific antigen (or PSA) from baseline.

The interim efficacy analysis of the trial demonstrated that ENV105, a first-in-class CD105 antagonist, in combination with standard of care hormone therapy apalutamide demonstrated a progression-free survival (PFS) of 13 months. Notably, the trial is powered to show a 45% improvement in the PFS. This translates to an increase in PFS from 3.7 to 6.7 months. This mark was far exceeded by the ENV105/ Apalutamide combination. The four-month timeframe is significant as 2nd or 3rd line standard of care hormone therapy has a 3.7 month median efficacy, as reported by the CARD trial (New Eng J. Med [2019] 381:2506). The same study also showed the use of chemotherapy (cabazitaxel) provided eight months’ PFS, by imaging, accompanied with greater toxicity.

"Our therapeutics, targeting cancer resistance, continue to showcase the potential to revolutionize the way we treat cancer patients," said Dr. John Yu, CEO of Kairos Pharma. "While this is only interim data, we are excited to bring together the principal investigators and other industry experts for an important event this afternoon to lay out the primary benefits of our compound, and demonstrate the clinical need filled by ENV105."

The randomized Phase 2 trial aims to enroll 100 patients in total and is presently accruing patients at Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Center. The study is designed to evaluate the safety, tolerability, and early signs of efficacy of ENV105, a CD105 antagonist, in men whose disease has progressed following standard hormone-based therapies.

The interim safety analysis of the same trial, announced in July of this year, demonstrated that ENV105 was well tolerated when combined with standard of care hormone therapy, apalutamide, from the first 10 enrolled patients. Thus far, there have been no dose-limiting toxicities or unexpected adverse events reported to date. In addition, the treatment-related side effects were manageable with standard supportive care. Notably, no Grade 3 or Grade 4 toxicities were observed.

Kairos Pharma will host a premier KOL event later today at 5 p.m. ET / 2 p.m. PT to discuss diverse perspectives on the interim efficacy results. Speakers at the KOL event include Dr. Neil Bhowmick, President and Chief Scientific Officer at Kairos Pharma; Dr. Umang Swami, Associate Professor in the Division of Oncology, Department of Internal Medicine at the Huntsman Cancer Institute; Dr. Richard Lee, Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers at Massachusetts General Hospital, Harvard Medical School; and Dr. Edwin Posadas, Director of the Experimental Therapeutics Program and the Medical Director of the Center for Uro-Oncology Research Excellence at the Cedars-Sinai Cancer Institute.

With one million men in the US diagnosed with prostate cancer each year, and millions more worldwide, the development of resistance to current hormone therapies has created a growing unmet need with an increasingly aging population. Castration-resistant prostate cancer refers to tumors that grow despite receiving hormone blocking agents. Treatment options remain limited after hormone therapies fail. Kairos Pharma seeks to provide a safe and effective alternative for these patients with ENV105.

On September 18, 2025 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the expansion of FLAMINGO-01 clinical trial to Ireland (Press release, Greenwich LifeSciences, SEP 18, 2025, View Source [SID1234656070]).

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The Company’s application to European regulators has been formally approved, adding Ireland as an approved country in FLAMINGO-01 in addition to Spain, France, Germany, Italy, Poland, Romania, and the US.

According to the latest data collected by the European Cancer Information System (click here), a total of 3,723 new cases of breast cancer were diagnosed in Ireland in 2022, which is the most common cancer diagnosed in women, representing approximately 30% of all cancers in women. Breast cancer is the 2nd leading cause of death from cancer in women in Ireland with 883 deaths in 2022.

The Company is collaborating with Dr. Janice Walshe, who will be serving as the national principal investigator in Ireland for FLAMINGO-01. She is a key member of Cancer Trials Ireland research group ensuring access to novel agents and research opportunities for Irish women affected by breast cancer. Through the clinical research clinic in St Vincent’s University Hospital in Dublin, Ireland, she has served as national principal investigator for many important international trials in breast cancer. She served as a three-year member of ASCO (Free ASCO Whitepaper) Scientific Program Committee in triple negative breast cancer from 2013-2015. Her research has been presented at numerous international meetings and published in prestigious peer reviewed journals.

CEO Snehal Patel commented, "We have visited St. Vincent’s multiple times over the past few years, once to present GP2 and FLAMINGO-01 at their conference and most recently to train the study team. We have also been approached by Irish breast cancer patients who wish to participate in FLAMINGO -01 and who can now be considered for enrollment through the Dublin site."

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US and European clinical sites from university-based hospitals and academic and cooperative networks with plans to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.