On December 12, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering precision immunotherapy for oncology and inflammation & immunology (I&I), reported initial clinical results from its ongoing STARt-002 phase 1b/2 trial during a late breaking presentation at the 2025 San Antonio Breast Cancer Symposium (SABCS) taking place December 9-12.

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Early findings from the combination study of Invikafusp alfa (Invika) and TRODELVY (sacituzumab govitecan-hziy; SG) suggest that this novel regimen, which leverages two key modalities (immunotherapy and ADCs), is well tolerated and biologically active across all dose levels evaluated. The safety profile of the combination was consistent with the known profiles of each agent.

"The early safety and pharmacodynamic data from STARt-002 are highly encouraging," said Steven Isakoff, M.D., Ph.D., Director of Breast Cancer Clinical Research at the Massachusetts General Hospital Cancer Center. "The combination of Invika with TRODELVY is scientifically compelling — pairing targeted T cell activation with ADC-mediated tumor killing. Seeing consistent Vβ6/10 expansion alongside early tumor responses reinforces the potential of this regimen to meaningfully benefit patients with metastatic breast cancer, and I look forward to the results from the ongoing phase 2 cohorts."

Pharmacodynamic analyses confirmed that Invika maintains its mechanism of action in combination with Trodelvy, inducing robust and selective expansion of Vβ6/10 T cells in patients with previously treated metastatic triple-negative breast cancer (TNBC) and HR+/HER2– metastatic breast cancer. Evidence of early anti-tumor activity was observed in almost all patients treated with this combination, including two confirmed partial responses.

A recommended phase 2 dose (RP2D) has now been established, and enrollment is ongoing in two phase 2 expansion cohorts for people with metastatic triple-negative breast cancer (TNBC) and HR+/HER2– metastatic breast cancer at select cancer centers across North America.

"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. "These initial findings further support Invika as a potential immunotherapy backbone, particularly when paired with ADCs to treat immunologically ‘cold’ tumors such as breast cancer. We are encouraged by the safety, pharmacology, and early signs of clinical activity observed with the Invika and SG regimen and look forward to understanding the full clinical potential of this treatment regimen as STARt-002 advances through Phase 2."

Additional presentation details are as follows:

Presentation: Initial clinical and pharmacology results from START-002
Abstract Number: LBA 3714
Presentation Number: PS4-06-28
Poster Presentation Date/Time: Thursday, December 11, 2025, 5:00 PM – 6:30 PM
Presentation: Trial-in-progress: START-002
Abstract Number: 2124
Presentation Number: PS5-09-16
Poster Presentation Date/Time: Friday, December 12, 2025, 12:30 PM – 2:00 PM
The combination of invikafusp alfa and sacituzumab govitecan-hziy is investigational and not approved by any health authority globally. The safety and efficacy of this combination has not been established.

(Press release, Marengo Therapeutics, DEC 12, 2025, View Source [SID1234661407])

On December 11, 2025 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, reported it has completed its targeted full enrollment of 435 patients in the registration-enabling Phase 2/3 trial (OptimUM-02) evaluating darovasertib, the company’s investigational oral protein kinase C (PKC) inhibitor, in combination with Pfizer’s crizotinib, an oral c-MET inhibitor, in first line (1L) HLA*A2-negative metastatic uveal melanoma (mUM). IDEAYA expects to report median progression-free survival (PFS) data from this trial in the first quarter 2026 to support a potential accelerated approval filing in the United States. Median overall survival (mOS) data from OptimUM-02, once available, will be used to support a potential full approval filing. Metastatic uveal melanoma is a rare, aggressive form of ocular cancer with limited treatment options and historically poor survival outcomes.

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"We are very pleased to announce that we have achieved the target enrollment to enable potential full approval filing in our Phase 2/3 registration-enabling trial of darovasertib in combination with crizotinib in first-line HLA*A2-negative metastatic uveal melanoma. This milestone reflects both the clear unmet need in metastatic uveal melanoma, as well as the strong clinical interest in our darovasertib program. Moreover, the promising overall survival data and broader clinical efficacy demonstrated in the recently reported median overall survival results from the Phase 1/2 clinical trial (OptimUM-01) of this combination in metastatic uveal melanoma are indicative of the clinical potential of darovasertib to meaningfully impact patients with this devastating disease. With target full enrollment now complete, we look forward to the availability of median PFS data we project from OptimUM-02 in the first quarter of next year, and, if approved, making darovasertib in combination with crizotinib available to patients with HLA*A2-negative metastatic uveal melanoma as a first-line treatment as expeditiously as possible," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

OptimUM-02 is a multi-arm, multi-stage, open-label Phase 2/3 trial with patients randomized to receive either the darovasertib and crizotinib combination or investigator’s choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). The primary endpoints are median PFS and median OS, which will be used to support a potential accelerated approval and full approval in the United States, respectively. In October 2025, IDEAYA presented data from its single-arm, Phase 2 trial (OptimUM-01) of the darovasertib and crizotinib combination at the Society for Melanoma Research (SMR) Congress that demonstrated a 21.1 month median OS and 7.0 months median PFS in 1L mUM, including both HLA*A2-negative and HLA*A2-positive patients.

Darovasertib has received U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation as neoadjuvant therapy in enucleation recommended primary uveal melanoma (UM) and Fast Track designation for darovasertib in combination with crizotinib in adult patients with metastatic UM. Darovasertib has also been designated as an Orphan Drug by the U.S. FDA in UM, including in metastatic UM. IDEAYA is currently enrolling patients in a pivotal Phase 3 trial of single-agent darovasertib in the neoadjuvant setting of primary UM (OptimUM-10).

(Press release, Ideaya Biosciences, DEC 11, 2025, View Source [SID1234661384])

On December 11, 2025 ViroMissile, Inc., a cancer immunotherapy company pioneering the IDOV (Intravenously Deliverable Oncolytic Virus) platform, reported the initiation of a first-in-human clinical trial evaluating IDOV-Immune, its investigational oncolytic vaccinia virus therapy, in patients with advanced solid tumors (NCT06910657). Additional trial sites across the United States are expected to begin enrolling in 2026, pending clearance of the U.S. IND. The first patient was dosed at The Alfred Hospital in Melbourne, Victoria, Australia.

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"Launching this first-in-human trial marks an important milestone for ViroMissile and our mission to reshape cancer immunotherapy with selective viruses that target tumors while sparing healthy tissue," said Nanhai George Chen, PhD, CEO and founder of ViroMissile. "IDOV-Immune was engineered to penetrate the tumor, destroy cancer cells directly, and activate a coordinated immune response against the disease in a convenient systemic dose. We are excited to begin evaluating this therapy in patients who have exhausted standard options and to advance a new class of immunotherapies that may meaningfully improve outcomes."

The Phase I, open-label, multi-center trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary anti-tumor activity of a single intravenous (IV) infusion of IDOV-Immune. The study plans to enroll up to 78 adult participants at study sites across the United States and Australia, including leading cancer centers. The primary objective is to determine the safety and tolerability of IDOV-Immune, including characterization of treatment-emergent adverse events (TEAEs) through Day 90 and dose-limiting toxicities (DLTs) during the first 28 days, and to determine the maximum tolerated dose and recommended dose for Phase 2 studies. Secondary objectives include evaluating the PK and PD profile of IDOV-Immune, characterizing immunologic responses and the development of neutralizing antibodies, and assessing preliminary signs of antitumor activity, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR) over a 12-month follow-up period.

Shah Rahimian, MD, chief medical officer at ViroMissile, added, "As we enroll patients into this first-in-human study, we are particularly encouraged by the opportunity to evaluate IDOV-Immune as a systemically administered oncolytic therapy. Delivering a single intravenous dose that can reach tumors throughout the body, while also activating both innate and adaptive immunity, represents an important evolution in the field. This trial will help us understand the safety profile, viral kinetics, and early biological activity of IDOV-Immune, and we are deeply grateful to the patients who make this work possible."

(Press release, ViroMissile, DEC 11, 2025, View Source [SID1234661462])

On December 11, 2025 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported initial clinical data from the Phase 1 portion of its ongoing Phase 1/2 clinical study of AVZO-021, its potential best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor. The initial data highlighted preliminary clinical activity, including objective responses across patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer and cyclin E1 (CCNE1)-amplified ovarian cancer. AVZO-021 was generally well tolerated with relatively low incidence and severity of gastrointestinal and hematologic adverse events, which are commonly observed adverse events associated with other CDK inhibitors.

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The findings were reported at the 2025 San Antonio Breast Cancer Symposium.

"CDK2 has emerged as an important resistance mechanism in patients with HR+/HER2- breast cancer, especially for patients who progress on CDK4/6 inhibitors," said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program and Diana Hyland Endowed Chair for Breast Cancer at University Hospitals Seidman Cancer Center, Case Western Reserve University. "These data reported today for AVZO-021 are exciting as they not only demonstrate the activity and tolerability of AVZO-021, but the potential for its use in combination with other agents."

AVZO-021, Phase 1 Initial Clinical Data

Utilizing an October 10, 2025 data cut-off date, 35 patients with advanced solid tumors were treated with AVZO-021 monotherapy across nine dose levels, and 10 patients with HR+/HER2- breast cancer were treated with AVZO-021 in combination with fulvestrant across two AVZO-021 dose levels.

The median number of prior therapies in the metastatic setting was 3.0 (range zero to 11), with all patients with HR+/HER2- breast cancer having received at least one prior CDK4/6 inhibitor.

Efficacy-evaluable patients included 19 patients with HR+/HER2- breast cancer or CCNE1-amplified solid tumors treated with AVZO-021 monotherapy doses of 150 mg once daily (QD) and above with at least one post-baseline scan, and nine patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant with at least one post-baseline scan.

As of the October 10, 2025 data cut-off date:

Initial Safety Results

A total of 45 patients comprise the safety population, including 35 patients with advanced solid tumors treated with AVZO-021 monotherapy at dose levels from 20 mg QD to 250 mg QD, and 10 patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant at AVZO-021 dose levels of 150 mg QD and 200 mg QD.
All-grade treatment emergent adverse events (TEAEs) reported in greater than 20 percent of patients were nausea (44%), fatigue (38%), anemia (33%), and vomiting (29%).
The majority of TEAEs were Grade 1 or Grade 2, and no patients had TEAEs leading to treatment discontinuation.
Initial Pharmacokinetic and Pharmacodynamic Results

PK data suggested continuous CDK2 target coverage was achieved at doses of 90 mg QD and above.
Comparable exposures of AVZO-021 were observed between AVZO-021 monotherapy and in combination with fulvestrant at 150 mg QD, indicating no drug-drug interaction.
Significant decreases in circulating tumor DNA (ctDNA) were observed.
Initial Efficacy Results

Of 19 efficacy-evaluable patients treated with AVZO-021 monotherapy, three patients experienced confirmed responses, including two with HR+/HER2- breast cancer with onset at weeks 15 and 36 and one with CCNE1-amplified ovarian cancer with onset at week 35. Seven patients, who remain on treatment, achieved stable disease, including six with HR+/HER2- breast cancer.
Of nine efficacy evaluable HR+/HER2- breast cancer patients treated with AVZO-021 in combination with fulvestrant, one patient experienced a confirmed response, with onset at week 7; the confirmatory scan was obtained after the data cut-off date. Three patients, who remain on treatment, achieved stable disease.
All responders remain on treatment with two on treatment for greater than 48 weeks.
"We are encouraged by the initial safety and efficacy data from this study, especially given multiple patients show improvement over time and remain on treatment," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "We look forward to advancing the development of AVZO-021 in combination with our highly potent and selective CDK4 inhibitor, AVZO-023."

In addition, the company presented the study design for the ongoing Phase 1/2 study evaluating AVZO-023, its potential best-in-class cyclin-dependent kinase 4 (CDK4) selective inhibitor, as a single agent and in combination with AVZO-021 and/or endocrine therapy at the 2025 San Antonio Breast Cancer Symposium.

(Press release, Avenzo Therapeutics, DEC 11, 2025, View Source [SID1234661368])

On December 11, 2025 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported the presentation of final data from the Phase 1 clinical trial of its investigational breast cancer vaccine (NCT04674306) at the 2025 San Antonio Breast Cancer Symposium (SABCS). The trial was conducted in collaboration with Cleveland Clinic and funded by a grant from the U.S. Department of Defense.

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Final Phase 1 findings showed the investigational vaccine met all major primary endpoints, was safe and well tolerated at the maximum tolerated dose (MTD), and elicited protocol-defined immune responses in 74% of participants. The presentation, titled "Final Results of a Phase I Trial of Alpha-lactalbumin (aLA) Vaccine for Breast Cancer," was delivered by Justin Johnson, Ph.D., Program Manager at Cleveland Clinic and co-inventor of the breast cancer vaccine technology. The SABCS poster presentation is available at View Source

"Triple-negative breast cancer remains one of the most challenging subtypes to address, and Phase 1 trials are an important step in determining whether a new approach can be administered safely and activate the immune system as intended," said G. Thomas Budd, M.D., of Cleveland Clinic’s Cancer Institute and principal investigator of the study. "In this trial, the investigational α-lactalbumin vaccine was safe and well tolerated at the maximum tolerated dose and generated protocol-defined immune responses in 74% of participants—results that support continued clinical evaluation."

Topline Phase 1 results:

All major primary endpoints were met
74% of participants demonstrated protocol-defined immune responses; α-lactalbumin (aLA)-specific T cell responses were observed per protocol-defined criteria
Vaccine was safe and well tolerated at the MTD, with adverse events primarily injection-site irritation
Preliminary Immunohistochemistry (IHC) of primary tumors showed aLA expression ranging from absent to strong; analyses correlating expression to immune response and clinical outcomes are ongoing
Participants will be followed for five years after completing the study
Combination of Keytruda and the vaccine also generated antigen-specific T cell responses and showed no major additional side effects
Data will inform planned Phase 2 study design, including a potential Phase 2 combination study with Keytruda in the neoadjuvant setting among newly diagnosed breast cancer patients
The Phase 1 study evaluated safety and monitored immune response to an investigational vaccine targeting α-lactalbumin (aLA). The trial enrolled 35 participants across three cohorts: Cohort Ia (n=26), women who completed standard-of-care treatment, including surgery, for early-stage TNBC within three years and were tumor-free but at elevated risk of recurrence; Cohort Ib (n=4), cancer-free women with BRCA1, BRCA2, or PALB2 mutations who elected preventive mastectomy and were vaccinated prior to surgery; and Cohort Ic (n=5), women with TNBC receiving pembrolizumab (Keytruda) in the adjuvant (post-surgery) setting, with evaluation of safety of combination administration and immune responses.

In Cohort Ia, at the MTD, the vaccine was reported as safe, with no flu-like symptoms (fever and myalgias), no abnormal clinical laboratory tests, and no other observed adverse side effects in this cohort; the primary notable adverse event was injection-site irritation. Participants demonstrated aLA-specific T cell responses, including production of interferon gamma and interleukin-17.

In Cohort Ib, safety and tolerability were similar to Cohort Ia. Immunohistochemistry analyses of resected breast tissue are ongoing and will be presented in a future scientific presentation.

In Cohort Ic, a key objective was to assess whether administration of the investigational vaccine in combination with pembrolizumab could create intolerable side effects. No major adverse side effects were reported; as in other cohorts, the primary adverse event was injection-site irritation. Two participants experienced Grade 3 adverse events consisting of greater irritation at an injection site.

The investigational vaccine targets α-lactalbumin, a lactation protein generally expressed in the breast during lactation but not at other times in life or in other normal tissues. In many breast cancers, malignant cells express α-lactalbumin. The vaccine is designed to activate the immune system to direct cytotoxic T cells toward tumor cells expressing α-lactalbumin, with the goal of providing preemptive immune protection against emerging tumors that express this antigen.

The vaccine is based on preclinical research led by the late Vincent Tuohy, Ph.D., who served as the Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research at Cleveland Clinic.

"It was Dr. Tuohy’s hope that this vaccine would demonstrate the potential of immunization as a new way to combat breast cancer, and that a similar approach could someday be applied to other types of malignancies," said Dr. Johnson. "Our findings that the majority of participants across all three cohorts demonstrated an immune response to α-lactalbumin is an encouraging sign."

Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences, stated, "We are very encouraged that the final Phase 1 data met all major primary endpoints, with the vaccine demonstrating a favorable tolerability profile at the MTD and protocol-defined immune responses in the majority of participants. We appreciate the support provided through the U.S. Department of Defense grant that enabled this study in collaboration with Cleveland Clinic, and we look forward to engaging with regulators and advancing plans for a Phase 2 study."

(Press release, Anixa Biosciences, DEC 11, 2025, View Source [SID1234661385])