Actinium Pharmaceuticals Announces Clinical Trial Program in Solid Tumors Combining Actimab-A with PD-1 Checkpoint Inhibitors KEYTRUDA® and OPDIVO®
Actinium Pharmaceuticals (NYSE: ATNM) has announced a new clinical trial program combining Actimab-A with PD-1 checkpoint inhibitors KEYTRUDA® and OPDIVO® for solid tumors. The trials aim to improve patient outcomes by targeting Myeloid Derived Suppressor Cells (MDSCs) in the tumor microenvironment, which currently limit PD-1 inhibitors' effectiveness.
The program includes controlled, head-to-head trials focusing on Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-Small Cell Lung Cancer (NSCLC). Initial proof of concept clinical data is expected in the second half of 2025. The company estimates a potential treatment population exceeding 500,000 patients.
The trials will evaluate safety, tolerability, Overall Response Rate (ORR), Progression Free Survival (PFS), and Overall Survival (OS). Actimab-A, which has been studied in over 150 AML patients, delivers Actinium-225, targeting CD33-expressing MDSCs.
Actinium Pharmaceuticals (NYSE: ATNM) ha annunciato un nuovo programma di sperimentazione clinica che combina Actimab-A con gli inibitori del checkpoint PD-1 KEYTRUDA® e OPDIVO® per i tumori solidi. Gli studi mirano a migliorare i risultati per i pazienti mirando alle Cellule Soppressive Derivate da Mieloidi (MDSC) nel microambiente tumorale, che attualmente limitano l'efficacia degli inibitori PD-1.
Il programma include studi controllati, testa a testa, focalizzati sul Carcinoma Squamoso della Testa e del Collo (HNSCC) e sul Carcinoma Polmonare Non a Piccole Cellule (NSCLC). I dati clinici iniziali di prova di concetto sono attesi nella seconda metà del 2025. L'azienda stima una popolazione potenziale di trattamento che supera i 500.000 pazienti.
Le sperimentazioni valuteranno la sicurezza, la tollerabilità, il Tasso di Risposta Globale (ORR), la Sopravvivenza Libera da Progressione (PFS) e la Sopravvivenza Globale (OS). Actimab-A, che è stato studiato in oltre 150 pazienti con AML, somministra Actinium-225, mirando alle MDSC che esprimono CD33.
Actinium Pharmaceuticals (NYSE: ATNM) ha anunciado un nuevo programa de ensayos clínicos que combina Actimab-A con los inhibidores de checkpoint PD-1 KEYTRUDA® y OPDIVO® para tumores sólidos. Los ensayos tienen como objetivo mejorar los resultados de los pacientes al dirigirse a las Células Supresoras Derivadas de Mieloides (MDSC) en el microambiente tumoral, que actualmente limitan la efectividad de los inhibidores de PD-1.
El programa incluye ensayos controlados, cara a cara, centrados en el Carcinoma de Células Escamosas de Cabeza y Cuello (HNSCC) y el Carcinoma Pulmonar No de Células Pequeñas (NSCLC). Se esperan datos clínicos iniciales de prueba de concepto en la segunda mitad de 2025. La empresa estima una población de tratamiento potencial que supera los 500,000 pacientes.
Los ensayos evaluarán la seguridad, la tolerabilidad, la Tasa de Respuesta Global (ORR), la Supervivencia Libre de Progresión (PFS) y la Supervivencia Global (OS). Actimab-A, que ha sido estudiado en más de 150 pacientes con AML, entrega Actinium-225, dirigiéndose a las MDSC que expresan CD33.
액티늄 제약 (NYSE: ATNM)은 액티맙-A와 PD-1 체크포인트 억제제 KEYTRUDA® 및 OPDIVO®를 결합한 새로운 임상 시험 프로그램을 발표했습니다. 이 시험은 PD-1 억제제의 효과를 제한하는 종양 미세환경의 골수 유래 억제 세포(MDSC)를 표적으로 하여 환자 결과를 개선하는 것을 목표로 합니다.
이 프로그램은 두경부 편평세포암(HNSCC) 및 비소세포 폐암(NSCLC)에 초점을 맞춘 통제된 직접 비교 시험을 포함합니다. 초기 개념 증명 임상 데이터는 2025년 하반기에 예상됩니다. 이 회사는 500,000명 이상의 잠재적 치료 인구를 추정하고 있습니다.
시험은 안전성, 내약성, 전체 반응률(ORR), 무진행 생존 기간(PFS) 및 전체 생존 기간(OS)을 평가할 것입니다. 액티맙-A는 150명 이상의 AML 환자에서 연구되었으며, CD33을 발현하는 MDSC를 표적으로 하는 액티늄-225를 전달합니다.
Actinium Pharmaceuticals (NYSE: ATNM) a annoncé un nouveau programme d'essais cliniques combinant Actimab-A avec les inhibiteurs de checkpoint PD-1 KEYTRUDA® et OPDIVO® pour les tumeurs solides. Les essais visent à améliorer les résultats des patients en ciblant les Cellules Suppresseurs Dérivées des Myéloïdes (MDSC) dans le microenvironnement tumoral, qui limitent actuellement l'efficacité des inhibiteurs PD-1.
Le programme comprend des essais contrôlés, en tête-à-tête, axés sur le Carcinome Épidermoïde de la Tête et du Cou (HNSCC) et le Carcinome Pulmonaire Non à Petites Cellules (NSCLC). Les premières données cliniques de preuve de concept sont attendues dans la seconde moitié de 2025. L'entreprise estime une population potentielle de traitement dépassant les 500 000 patients.
Les essais évalueront la sécurité, la tolérabilité, le Taux de Réponse Global (ORR), la Survie Sans Progression (PFS) et la Survie Globale (OS). Actimab-A, qui a été étudié chez plus de 150 patients atteints de LMA, délivre de l'Actinium-225, ciblant les MDSC exprimant CD33.
Actinium Pharmaceuticals (NYSE: ATNM) hat ein neues klinisches Studienprogramm angekündigt, das Actimab-A mit den PD-1-Checkpoint-Inhibitoren KEYTRUDA® und OPDIVO® für solide Tumoren kombiniert. Die Studien zielen darauf ab, die Ergebnisse für die Patienten zu verbessern, indem sie die myeloid-abgeleiteten Suppressorzellen (MDSCs) im Tumormikroenvironment anvisieren, die derzeit die Wirksamkeit der PD-1-Inhibitoren einschränken.
Das Programm umfasst kontrollierte, direkte Vergleichsstudien, die sich auf Plattenepithelkarzinome im Kopf- und Halsbereich (HNSCC) und nicht-kleinzelliges Lungenkarzinom (NSCLC) konzentrieren. Erste klinische Daten als Nachweis des Konzepts werden in der zweiten Hälfte des Jahres 2025 erwartet. Das Unternehmen schätzt eine potenzielle Behandlungsbevölkerung von über 500.000 Patienten.
Die Studien werden Sicherheit, Verträglichkeit, die Gesamtansprechrate (ORR), das progressionsfreie Überleben (PFS) und das Gesamtüberleben (OS) bewerten. Actimab-A, das bei über 150 AML-Patienten untersucht wurde, liefert Actinium-225 und zielt auf CD33-exprimierende MDSCs ab.
- Large market opportunity with over 500,000 potential patients
- Novel approach targeting MDSCs could improve efficacy of established blockbuster drugs (KEYTRUDA® and OPDIVO®)
- Strong safety profile with Actimab-A already tested in 150+ patients
- Multiple clinical trials planned across different solid tumor types
- Initial clinical proof of concept data not available until late 2025
- No guarantee of successful trial outcomes or MDSC depletion in humans
- Competing in established market against major pharmaceutical companies
Insights
Actinium Pharmaceuticals' announcement represents a strategic expansion of their radiotherapeutic Actimab-A into solid tumors, which dramatically increases their addressable market. The scientific rationale is compelling - Actimab-A targets CD33+ myeloid-derived suppressor cells (MDSCs) which are known to inhibit T-cell function and limit efficacy of PD-1 checkpoint inhibitors like KEYTRUDA® and OPDIVO®.
The clinical approach is particularly noteworthy for three reasons: First, it leverages Actimab-A's established safety profile from over 150 AML patients; second, it targets a well-documented immunosuppressive mechanism in the tumor microenvironment; third, it's designed as controlled head-to-head trials against standard of care immunotherapies. The company is effectively positioning Actimab-A as a potential combination backbone therapy across multiple solid tumor indications.
The targeted treatment population exceeding 500,000 patients represents an enormous opportunity relative to Actinium's current
This clinical program announcement represents substantial upside potential for Actinium Pharmaceuticals. The company is strategically targeting a significant unmet need in the $38.8 billion PD-1 inhibitor market by addressing a known resistance mechanism.
For a micro-cap company (
The program leverages the company's existing Actimab-A asset, which has been derisked from a safety perspective through extensive testing in AML, creating efficient R&D capital allocation. Initial proof-of-concept data expected in H2 2025 provides a relatively near-term catalyst that could drive significant valuation reassessment.
While early-stage, this approach targeting the tumor microenvironment represents a differentiated strategy in the crowded immuno-oncology landscape. If successful in enhancing PD-1 inhibitor efficacy, Actimab-A could potentially command premium pricing as a combination therapy across multiple solid tumor indications with a treatment population exceeding 500,000 patients.
- Trials are designed to demonstrate whether the addition of Actimab-A to either KEYTRUDA® or OPDIVO® can result in improved patient outcomes
- MDSCs – Myeloid Derived Suppressor Cells in the tumor microenvironment are believed to reduce effectiveness of PD-1 inhibitors like KEYTRUDA® and OPDIVO®
- Trials supported by preclinical data showing Actimab-A can selectively target and deplete MDSCs which express CD33
- Clinical proof of concept data expected in 2025 could potentially open up a multi-billion-dollar market opportunity for Actimab-A as a combination therapy with PD-1 inhibitors in multiple solid tumors
MDSCs are immune-suppressive cells that help tumors evade immune detection and promote disease progression. They are overexpressed in the tumor microenvironment in several different solid tumors and associated with poor outcomes. They work by multiple mechanisms but most relevant to PD-1 inhibitors which work by keeping T-cells active is that MDSCs prevent T-cells from recognizing and attacking cancer cells. There is considerable preclinical scientific evidence in the literature that depleting MDSCs could be a viable strategy in improving the outcomes of PD-1 directed immunotherapy, however, there have been no viable clinical approaches that have been tried successfully to our knowledge. MDSCs are known to express the CD33 antigen which is the target of Actimab-A. Actinium has also generated published and unpublished preclinical data showing that Actimab-A can selectively deplete MDSCs in solid tumors. Actinium believes that in the clinic Actimab-A can deplete CD33 expressing MDSCs and hence improve the outcomes with PD-1 inhibitors such as KEYTRUDA® and OPDIVO®.
Actimab-A is Actinium's lead radiotherapeutic that delivers Actinium-225, a potent alpha-emitter radioisotope payload that can produce lethal double strand DNA breaks to kill targeted cells. Actimab-A has been studied in over 150 patients in several clinical trials in Acute Myeloid Leukemia or AML. Based on its safety and tolerability, Actimab-A is under clinical development via an NCI CRADA in the front-line AML setting with an expected registrational study in combination with CLAG-M in relapsed/refractory AML expected to initiate in 2025.
The Actimab-A solid tumor program is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA® versus KEYTRUDA® alone, and Actimab-A with OPDIVO® versus OPDIVO® alone. The initial tumors that are being targeted are HNSCC or Head and Neck Squamous Cell Carcinoma and NSCLC or Non-Small Cell Lung Cancer with a separate trial for each indication. The patient population for these trials will be adults with PD-L1 expression and locally advanced metastatic HNSCC or NSCLC randomized to either Actimab-A alone or Actimab-A with a specific checkpoint inhibitor. The objective of each trial would be to evaluate the safety and tolerability as well as following endpoints including ORR – Overall Response Rate, PFS – Progression Free Survival and OS – Overall Survival. Further, the following biomarker data would be collected including the pattern of depletion of CD33+ MDSCs and T-Cell activity in peripheral blood. Actinium expects to present initial proof of concept clinical data from the first of these trials in the second half of 2025 as well as provide an update on the outlook for the rest of the trials in the Actimab-A solid tumor program.
Dr. Avinash Desai, Actinium's Chief Medical Officer, said, "The Actimab-A solid tumor program is highly novel and has the potential to address the high unmet need of patients receiving PD-1 checkpoint inhibitors whose cancer stops responding or progresses. Our preclinical data is highly encouraging and we believe this novel approach combining Actimab-A with PD-1 inhibitors has immense potential. We are greatly enthusiastic about these head-to-head trials, and eager to present our initial proof-of-concept results by the end of 2025."
Sandesh Seth, Actinium's Chairman and CEO, said, "We have great enthusiasm for Actimab-A in combination with PD-1 checkpoint inhibitors given the large potential addressable patient population. MDSCs are over expressed in multiple solid tumors giving Actimab-A pan tumor potential in indications that are treated with checkpoint inhibitors. Per our initial estimates this represents a treatment population in excess of 500,000 patients. Together with our efforts in myeloid malignancies, this is another important program for Actimab-A. This year, clinical data from Actimab-A as a potential backbone therapy in radiation sensitive myeloid malignancies, and in solid tumors in combination with PD-1 checkpoint inhibitors, can establish its potential to become a leading blockbuster targeted radiotherapy."
About Actinium Pharmaceuticals, Inc.
Actinium is a pioneer in the development of targeted radiotherapies intended to meaningfully improve patient outcomes. Actinium is advancing its lead product candidate Actimab-A, a CD33 targeting therapeutic, as potential backbone therapy in acute myeloid leukemia (AML) and other myeloid malignancies leveraging the mutation agnostic alpha-emitter radioisotope payload Actinium-225 (Ac-225). Actimab-A has demonstrated potential activity in relapsed and refractory acute myeloid leukemia (r/r AML) patients in combination with the chemotherapy CLAG-M including high rates of Complete Remissions (CR) and measurable residual disease (MRD) negativity leading to improved survival outcomes and is being advanced to a pivotal Phase 2/3 trial. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. The first clinical trial under the CRADA will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients. Additionally, Actinium is developing Actimab-A as a potential pan tumor therapy in combination with PD-1 checkpoint inhibitors including KEYTRUDA® and OPDIVO® by depleting myeloid derived suppressor cells (MDSCs), which represents a potential multi-billion-dollar addressable market. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with r/r AML, which Actinium is seeking a potential strategic partner for in the
For more information, please visit: https://www.actiniumpharma.com/
Forward-Looking Statements
This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.
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