On October 6, 2025 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the first patient has been treated in the Company’s OTS program, with encouraging preliminary safety data (Press release, Marker Therapeutics, OCT 6, 2025, View Source [SID1234656461]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Marker is evaluating the safety and efficacy of escalating doses of MT-401, a multi-antigen recognizing (MAR) T cell product targeting four antigens, as an OTS product in the Phase 1 RAPID study (clinicaltrials.gov Identifier: NCT06552416). The first study participant received the OTS product at the initial dose level (100×106 cells) and was monitored for 28 days. The therapy was well tolerated with no treatment-related adverse events. This observation is consistent with the favorable safety profile and tolerability previously reported for MAR-T cells. The OTS product will be initially tested in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), with the potential to be expanded to other indications.

"The initiation of our OTS program represents a major achievement," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "One of the biggest limitations to cell therapy is the time-consuming manufacturing of individualized products. With our OTS product, we are aiming to remove this bottleneck and provide a fast treatment option for patients with aggressive and rapidly progressing diseases. We believe that using commercially available leukapheresis material from healthy donors can facilitate large-scale manufacturing and expedite treatment as fast as 72 hours, while also enabling broader scalability and accessibility of cell therapies at a lower per-dose cost."

"Having a rapid available alternative to individualized T cell production allows us to broaden our clinical investigation of MAR-T cells and to extend the OTS program to other indications," commented Dr. Vera. "Looking ahead, we will remain focused on advancing our clinical investigation of MAR-T cells in lymphoma. We recently reported promising clinical efficacy and durability data from our APOLLO study where we have observed an objective response rate of 66%, with durable complete responses in patients with non-Hodgkin lymphoma, and we believe our lymphoma program has the potential to qualify for expedited approval."

Marker has secured non-dilutive funding from the Food and Drug Administration (FDA), the National Institutes of Health (NIH) Small Business Innovation Research (SBIR) program and the Cancer Prevention and Research Institute of Texas (CPRIT) to support the clinical investigation of the OTS product. Using these allocated non-dilutive funds will allow the Company to proceed with the OTS program without affecting the Company’s runway and its efforts to advance its lead asset, MT-601, in the ongoing Phase 1 APOLLO study in patients with lymphoma. Marker recently reported an update from the APOLLO study (Press Release, August 26, 2025) highlighting a favorable safety profile and durable clinical responses.

To facilitate the OTS program, the Company has established a cellular inventory from commercially available leukapheresis material that was carefully selected to cover a large patient population with partially human leukocyte antigen (HLA) matched material. This approach has been validated and extensively tested in the clinic (Leen et al., Blood, 2013; Tzannou et al, Blood Adv, 2019; Tzannou et al, J Clin Oncol, 2017). Data from the ongoing RAPID trial will help inform future clinical developments of MAR-T cell products and guide their potential use as an OTS product in other indications.

"Behind this milestone is a set of scientific data and a significant body of research and development. This strategy has been tested extensively in the clinic at Baylor College of Medicine in the context of virus-specific T cells (VST). As we enroll additional patients in the Phase 1 RAPID study, we will continue to closely monitor the safety and long-term treatment effects of our OTS product. The collected data from this trial will serve as a foundation for refining and understanding the performance of MAR-T cells as an OTS product to potentially expand the OTS approach to other product candidates in our pipeline with the goal to accelerate time to treatment in other indications," concluded Dr. Vera.

About MAR-T cells

The multi-antigen recognizing (MAR) T cell platform (formerly known as multiTAA-specific T cells) is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Unlike other T cell therapies, MAR-T cells allow the recognition of hundreds of different epitopes within up to six tumor-specific antigens, thereby reducing the possibility of tumor escape. Since MAR-T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with an improved safety profile compared to current engineered T cell approaches and may provide patients with meaningful clinical benefits.

About the Off-the-Shelf Program

MT-401-OTS is an Off-the-Shelf (OTS) multi-antigen recognizing (MAR) T cell product that targets four different tumor antigens upregulated in cancer cells (Survivin, PRAME, NY-ESO-1, WT-1). MT-401-OTS is currently investigated in the Company-sponsored Phase 1 multicenter, open-label RAPID trial (clinicaltrials.gov identifier: NCT06552416) for the treatment of patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The Company’s OTS program is supported by the National Cancer Institute of the National Institutes of Health (Award Number 1R44CA285177), the Food and Drug Administration Department of Health and Human Services (R01FD007272), and the Cancer Prevention and Research Institute of Texas (CPRIT, Award Number DP210042).

On October 6, 2025 Biomed Valley Discoveries (BVD), a clinical-stage biotechnology company guided by its founders’ intent of bringing hope for life to patients, reported that results from a Phase 1b study investigating the safety and synergistic effects of intratumoral injection of Clostridium novyi-NT in combination with pembrolizumab in patients with advanced solid tumors were recently published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). Conducted in collaboration with researchers at The University of Texas MD Anderson Cancer Center, the Phase 1b study demonstrated an overall objective response rate (ORR) of 25% (n=4) among patients with various advanced solid tumor malignancies. These findings build upon results from an earlier Phase 1 study that demonstrated encouraging safety, tolerability, and anti-tumor results with CNV-NT monotherapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BVD is researching Clostridium novyi-NT (non-toxic) (CNV-NT/BVD-550) – an attenuated form of the Clostridium novyi, or C. novyi, bacteria – as a modality to target the necrotic cores of tumors and unleash a powerful tumor-destroying attack. C. novyi is a spore-forming, anaerobic bacterium that can only thrive in hypoxic regions (regions that lack oxygen) such as the necrotic core of a tumor. The consequence of germination and growth of CNV-NT results in direct tumor destruction as well as activation of the host immune system.

"A cancer-fighting presence in the necrotic cores of tumors is critical because current standard-of-care therapies typically do not destroy all cancer cells within these regions. This may, in turn, contribute to cancer’s growth and progression. CNV-NT can uniquely target and destroy typically difficult-to-access necrotic cores in tumors," said Brent Kreider, Ph.D., President of BVD and a co-author of the publication. "The powerful anti-cancer benefit of bacteria-based therapy was demonstrated well over a century ago. With the publication of these new data, we are excited to reinforce the potential of this approach to address critical unmet needs of cancer patients who may have few other treatment options."

"The innate immune response we observed with CNV-NT in the Phase 1 monotherapy trial suggested that pairing this therapeutic modality with an immunotherapy like pembrolizumab could amplify and enhance the durability of its cancer-fighting attack. The encouraging early data on this combination study support this hypothesis," said Sarina Piha-Paul, M.D., professor, of Investigational Cancer Therapeutics at MD Anderson, and corresponding author of the publication.

Study Design and Results

A total of 16 patients with advanced solid tumors were enrolled in the Phase 1b study. Patients received a single intratumoral injection of C. novyi-NT on day 8 across four dose cohorts (3 × 104 to 100 × 104 spores) with pembrolizumab (200 mg intravenously) every 3 weeks, day 0–24 months.

The combination therapy was generally well tolerated, with one grade 3 dose-limiting toxicity of abscess formation. The remainder of treatment-related adverse events, observed in ≥10% of patients, were grade 1 or 2 and included injection site reaction, pyrexia, pruritus, leukopenia, and anemia. The maximum tolerated dose was determined to be 200 mg pembrolizumab every 3 weeks and a single dose of 100 × 104 C.novyi-NT spores.

The confirmed ORR of 25% was observed among four patients with various tumor types, including nonkeratinizing undifferentiated nasopharyngeal squamous carcinoma, human papilloma virus–positive squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma (a rare cancer that originates in the bones of the spine or the skull). Among these patient responders, three partial responses and one complete response were observed, with a median duration of response of 10.93 months. Stable disease was observed in 69% of patients.

"With promising therapeutic viability data now in hand for CNV-NT as both a monotherapy and a combination therapy, we are evaluating possible partnerships for the next stage of development," said Dr. Kreider.

(Press release, BioMed Valley Discoveries, OCT 6, 2025, View Source [SID1234665997])

On October 6, 2025 Nanoligent reported the completion of a €12 million Series A financing round led by Inveready (Inveready Biotech IV), with participation from CDTI (through the Innvierte program), Clave Capital (Clave Innohealth), and existing investors i&i Biotech Fund I, Italian Angels for Growth / Nanolinvest, and AVANTECA Partners (Press release, Nanoligent, OCT 6, 2025, https://www.nanoligent.com/nanoligent-closes-12-million-series-a-financing-to-advance-its-lead-oncology-nanodrug/ [SID1234656462]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The proceeds will support completion of the regulatory preclinical package for the company’s lead candidate, NNL1524, enable manufacturing scale-up, and fund the initiation of a Phase Ia clinical study in patients with solid tumors.

NNL1524 is a multivalent cytotoxic nanoparticle designed to selectively target the chemokine receptor CXCR4, a protein involved in tumor growth, invasion, and metastasis, and frequently overexpressed in several hematologic and solid malignancies including colorectal, lung, and breast cancers. In preclinical studies, NNL1524 demonstrated significant antitumor activity as a single agent and a favorable safety profile, supporting its advancement into clinical development.

Dr. Montserrat Cano, Chief Executive Officer of Nanoligent, commented:
"This financing represents an important milestone for Nanoligent. The support of such a strong syndicate of investors will be instrumental as the company progresses toward clinical validation of its technology and first-in-human studies."

Antonio Herce, Director of Investments at Inveready, stated:
"Nanoligent’s nanodrug platform offers a distinctive approach to targeted cytotoxic therapy, combining high selectivity, internalization efficiency, and stability. We are pleased to support the company’s efforts to bring this promising technology closer to patients."

The transaction was advised by Hoffmann Eitle and VentureTech Audit.

On October 6, 2025 Daiichi Sankyo reported positive topline results from the TROPION-Breast02 phase 3 trial showed DATROWAY (datopotamab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progressionfree survival (PFS) compared to investigator’s choice of chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) for whom immunotherapy was not an option.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Approximately 70% of patients with metastatic TNBC are not candidates for immunotherapy, including all patients whose tumors do not express PD-L1 as well as patients with PD-L1 expressing tumors who cannot receive immunotherapy due to other factors.1 Chemotherapy remains the first-line standard of care for these patients.

"DATROWAY is the first antibody drug conjugate and the only therapy to significantly improve overall survival compared to chemotherapy in patients with metastatic triple negative breast cancer for whom immunotherapy is not an option," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "These landmark results from TROPION-Breast02 strengthen our confidence in our ongoing clinical development program for DATROWAY in triple negative breast cancer and other tumor types. We look forward to 2 discussing these data with global regulatory authorities and to bringing DATROWAY to patients with triple negative breast cancer as soon as possible."

"TROPION-Breast02 is the only trial ever to show an overall survival benefit in the first-line treatment of patients with metastatic triple negative breast cancer for whom immunotherapy is not an option," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "We expect today’s results will mark an inflection point in the treatment of these patients who have the poorest prognosis of any type of breast cancer and urgently need better options."

The safety profile of DATROWAY was consistent with previous clinical trials of DATROWAY in breast cancer. These data from TROPION-Breast02 will be presented at an upcoming medical meeting and shared with regulatory authorities.

Daiichi Sankyo and AstraZeneca are evaluating DATROWAY across stages and treatment settings of TNBC in three additional phase 3 trials. TROPION-Breast03 is evaluating DATROWAY as adjuvant therapy with or without AstraZeneca’s anti-PD-L1 therapy durvalumab versus investigator’s choice of therapy in patients with stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. TROPIONBreast04 is evaluating neoadjuvant DATROWAY plus durvalumab versus neoadjuvant pembrolizumab plus chemotherapy in patients with stage II-III triple negative or hormone receptor (HR) low, HER2 low or negative breast cancer. TROPION-Breast05 is evaluating first-line DATROWAY with or without durvalumab versus investigator’s choice of therapy in patients with metastatic TNBC whose tumors express PD-L1.

About TROPION-Breast02

TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of DATROWAY versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumors did not express PD-L1 as well as patients with PD-L1 expressing tumors who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as brain metastases.

The dual primary endpoints of TROPION-Breast02 are PFS assessed by blinded independent central review and OS. Key secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov

About Triple Negative Breast Cancer

TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.3,4 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.5,6,7 Metastatic TNBC is the most aggressive type of breast cancer and has the worst prognosis, with median overall survival of just 12 to 18 months and only about 14% of patients living five years following diagnosis.

While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.5 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.5 For patients with metastatic disease with PDL1 expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the firstline setting.10,11 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the first-line standard of care.

TROP2 is a protein broadly expressed in several solid tumors, including TNBC. TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer.

About DATROWAY

DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

DATROWAY (6 mg/kg) is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

DATROWAY (6 mg/kg) is approved in Russia and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFRdirected therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the DATROWAY Clinical Development Program

A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other cancer treatments in various settings.

(Press release, Daiichi Sankyo, OCT 6, 2025, View Source [SID1234665028])

On October 6, 2025 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking approval for Orca-T, its lead investigational allogeneic T-cell immunotherapy, for the treatment of hematological malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS) (Press release, Orca Bio, OCT 6, 2025, View Source;utm_medium=rss&utm_campaign=orca-bio-announces-fda-acceptance-and-priority-review-of-the-biologics-license-application-bla-for-orca-t-to-treat-hematological-malignancies [SID1234656463]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

"A stem cell transplant has been the only potentially curative option for many people with AML, ALL or MDS, however treatment-related toxicities too often hinder patient recovery. Acceptance of the Orca-T BLA marks a pivotal moment in our ability to deliver a first-in-class therapy designed to improve survival free from complications like graft versus host disease," said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio. "Supported by positive Phase 3 clinical data, today’s regulatory milestone reflects important recognition of the transformative potential of Orca-T. We look forward to working collaboratively with the FDA on the review of our application with the goal of advancing Orca-T and making it available to patients in need."

The BLA submission for Orca-T is supported by positive results from the pivotal Phase 3 study, Precision-T (NCT04013685), a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca-T compared to conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with AML, ALL and MDS. The study met its primary endpoint of a statistically significant improvement in survival free of moderate-to-severe chronic graft versus host disease (cGvHD) with Orca-T versus alloHSCT.

About Orca-T
Orca-T is an investigational allogeneic T-cell immunotherapy being evaluated for the treatment of multiple hematological malignancies including acute leukemias and myelodysplastic syndromes. Orca-T is composed of highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designation for the prevention of graft versus host disease or death in patients eligible for hematopoietic stem cell transplant from the U.S. Food and Drug Administration.