On March 17, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported that results from the clinical trial evaluating Actimab-A in combination with the chemotherapy CLAG-M in patients with relapsed/refractory acute myeloid leukemia (r/r AML) have been published in the peer-reviewed journal Leukemia (Press release, Actinium Pharmaceuticals, MAR 17, 2025, View Source [SID1234651197]). The publication highlights data including long-term survival outcomes from two-year follow-up and better outcomes in high-risk patients. Actimab-A is a novel targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33, a marker expressed ubiquitously on AML blasts. The trial was conducted at the Medical College of Wisconsin (MCW) which has extensive experience treating relapsed refractory AML patients with CLAG-M.

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Actimab-A + CLAG-M Trial Data Highlights from Publication:

18.4 month median Overall Survival (OS) in patients who received 1 or 2 lines of prior therapy
52% of patients in the Actimab-A +CLAG-M trial had TP53 mutations, 56% had prior allogeneic stem cell transplant and 56% of patients had prior Venetoclax therapy
Actimab-A + CLAG-M outcomes compare favorably to the results from historical data with CLAG-M alone in the pre-Venetoclax era from MCW’s study (median OS of 13.3 months). Typically, patients who have failed Venetoclax treatment demonstrate median survival between 2.4 – 4.6 months as reported in the literature and the patients with a TP53 mutation even have more dismal survival outcomes. Hence this data supports the use of Actimab-A plus CLAG-M for these patients.
Actimab-A + CLAG-M produced high rates of measurable residual disease negativity (MRD-) including 75% across all patients, 83.3% in patients with a TP53 mutation and 100% in patients with prior Venetoclax therapy
71% of eligible patients received a bone marrow transplant (BMT) and median OS in these patients was 24.05 months
Dr. Sameem Abedin, Associate Professor of Medicine at the Medical College of Wisconsin and Principal Investigator of the Actimab-A + CLAG-M study said, "We are delighted that the Actimab-A + CLAG-M results have been published in the peer-reviewed journal Leukemia. Despite advancements in treatment, patients with r/r AML, particularly those with high-risk features including TP53 mutations and prior Venetoclax therapy like those in our study, continue to have dismal outcomes and limited treatment options. We are excited that the combination of Actimab-A and CLAG-M produced high response rates with deep remissions including high rates of MRD negativity, improving access to potentially curable BMT resulting in enhanced survival outcomes. Importantly, we observed that responses were retained in high-risk patients. We believe these results support the utility of targeted radiotherapy for the treatment of AML and its mutation agnostic mechanism of action. We look forward to the initiation of the Phase 2/3 trial of Actimab-A + CLAG-M and further advancing this potentially important therapeutic modality in this patient population with a high unmet need."

Actinium has aligned with the FDA on a pivotal Phase 2/3 operationally seamless trial that will study Actimab-A + CLAG-M in r/r AML patients. The trial will optimize the dose of Actimab-A in combination with CLAG-M, that will be studied in the Phase 3 portion of the trial, which will be a randomized trial comparing overall survival and other outcomes of patients with r/r AML receiving Actimab-A + CLAG-M to CLAG-M alone. The trial is expected to be initiated in 2025.

Sandesh Seth, Actinium’s Chairman and CEO, said, "There is significant momentum for Actimab-A with the publication of these positive results in Leukemia and the recent initiation of the frontline AML triplet combination with Venetoclax and the hypomethylating agent ASTX-727 under our NCI CRADA. Actinium is committed to addressing the needs of the over 100,000 patients with AML and MDS in the U.S. and Europe with Actimab-A to realize its multi-billion-dollar market opportunity. Over the course of 2025, we expect to generate additional clinical data further supporting Actimab-A’s mutation agnostic, backbone therapy potential for radiation sensitive myeloid malignancies."

On March 17, 2025 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (NASDAQ: ALLR), a Phase 2 clinical-stage pharmaceutical company dedicated to developing stenoparib—a differentiated dual PARP/Wnt pathway inhibitor— reported the presentation of new clinical data from its ongoing Phase 2 trial with stenoparib monotherapy in advanced Ovarian Cancer at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer, held March 14-17 in Seattle, Washington (Press release, Allarity Therapeutics, MAR 17, 2025, View Source [SID1234651196]). SGO is the world’s premier organization for professionals working to lessen the impact of gynecologic cancers, and the Annual Meeting on Women’s Cancer is the premier educational and scientific event for gynecologic oncologists and others dedicated to advancing gynecologic cancer care.

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The poster presentation, titled "A Phase II Trial of Stenoparib (2X-121): A Novel Dual Tankyrase and PARP Inhibitor in Advanced, Recurrent Ovarian Cancer," will be presented by Dr. Fernanda B. Musa, MD, MS, Director of Clinical Trials in Gynecologic Oncology, Providence-Swedish Cancer Institute.

Session: Poster Tour Group 14: Clinical Trials Impacting Future Therapies
Date/Time: Monday, March 17, 10:30 a.m. PST
The poster presents data from the first Phase 2 study of stenoparib in advanced ovarian cancer and the first stenoparib study ever to dose twice daily. The study exclusively enrolled patients who had been previously treated with three or more lines of therapy and included patients with especially difficult-to-treat disease. Fourteen of the fifteen enrolled were platinum-resistant, while one patient had primary platinum-refractory disease that did not respond to first-line chemotherapy. There are very few effective treatment options for patients with platinum-resistant and refractory ovarian cancer, who unfortunately tend to have their disease recur within an average of three months. In this study, five patients stayed on therapy longer than four months, with four of these staying on beyond 20 weeks. Importantly, one patient showed a confirmed complete response (i.e., absence of measurable disease) that lasted more than 10 months. The patient with primary platinum-refractory disease remained on therapy beyond 40 weeks. Two patients remain on therapy currently—now more than 17 months.

The data also revealed significant clinical benefit in patients who typically do not get benefit from first-generation PARP inhibitors—those without mutations in the DNA repair gene, BRCA. One of the two patients still on therapy, now more than 17 months, did not have a BRCA mutation or other deficit in homologous DNA repair. Benefit in these BRCA wild-type patients may reflect the unique, dual therapeutic action of stenoparib in inhibiting not only PARP but also the Wnt pathway—a pathway activated in ovarian, colon, and other advanced cancers.

Key Findings:

First study to dose stenoparib twice daily optimizing inhibition of PARP and Tankyrase across every 24-hour period.
First stenoparib study to show potential durable clinical benefit in platinum-resistant and refractory patients.
Data continue to show that stenoparib is well-tolerated and does not elicit the bone marrow toxicity typical of first-generation PARP inhibitors.
Study shows clinical benefit across distinct genetic backgrounds including in both BRCA-mutant patients and in BRCA wild-type (non-mutated) patients, a larger patient group than those with BRCA mutation.
Study supports the unique mechanism of action for stenoparib, which inhibits PARP and the Wnt oncogenic pathway.
Study sets the stage for the newly announced protocol to evaluate stenoparib monotherapy dosed twice daily in platinum-resistant patients.
Dr. Fernanda B. Musa, MD, MS, site investigator for the study, commented, "This remains a challenging disease with limited therapies for patients who have already undergone many prior lines of treatment and who have been declared platinum-resistant or platinum-refractory. The findings from this study suggest that stenoparib may offer a new, well-tolerated therapeutic approach for a broader group of patients, including those with BRCA wild-type disease, who historically have had fewer options. It is a privilege to present these data at SGO 2025 and to share our findings with esteemed colleagues dedicated to advancing gynecologic oncology research."

Thomas Jensen, Chief Executive Officer of Allarity Therapeutics, stated, "These results are foundational for us as they show stenoparib monotherapy can provide durable clinical benefit to very heavily pre-treated patients, both platinum-resistant and refractory. These data also show clinical benefit in patients both with and without BRCA mutations, or defects in homologous DNA damage repair, and may reflect the unique dual action of stenoparib on both PARP and Tankyrase targets. The data also continue to show that stenoparib is well-tolerated and does not show the bone marrow toxicity of earlier PARP inhibitors. All in all, the results of this exploratory phase 2 study have helped us to craft a new protocol designed with Dr. Fernanda Musa, Dr. Kathleen Moore, and other ovarian cancer thought leaders that will deepen and enrich our understanding of stenoparib’s durable clinical benefit—even in heavily pre-treated patients, enhance our understanding of its unique mechanism of action and accelerate the advance of stenoparib toward regulatory approval."

Given the relatively heterogeneous patient population in this study, there are no direct comparisons to earlier studies. Importantly, this exploratory trial allowed enrollment of patients with very advanced disease, including massive ascites, following multiple prior lines of therapy. Some of these patients progressed very quickly in the study. The recently announced phase 2 protocol trial was expressly designed to narrow in on patients with platinum-resistant disease who have progressed through only a single, additional line of chemotherapy after the emergence of platinum resistance and who are without active evidence of ascites.

The poster presentation will be available on March 17 at 7:00 a.m. CT on Allarity’s website under the Scientific Publications section.

About Stenoparib
Stenoparib is an orally available, small-molecule dual-targeted inhibitor of PARP1/2 and tankyrase 1/2. At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in regulating the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of numerous cancers. By inhibiting PARP and blocking Wnt pathway activation, stenoparib’s unique therapeutic action shows potential as a promising therapeutic for many cancer types, including ovarian cancer. Allarity has secured exclusive global rights for the development and commercialization of stenoparib, which was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121.

On March 17, 2025 AstraZeneca and Alteogen Inc. reported to have entered into an exclusive license agreement for ALT-B4, a novel hyaluronidase utilising Hybrozyme platform technology (Press release, AstraZeneca, MAR 17, 2025, View Source [SID1234651195]). Under the terms of the agreement, AstraZeneca will acquire worldwide rights to use ALT-B4 to develop and commercialise subcutaneous formulations of several oncology assets. Alteogen will be responsible for clinical and commercial supply of ALT-B4 to AstraZeneca.

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Subcutaneous formulations have the potential to offer many advantages including time savings for patients, clinical staff, and health systems due to shorter administration times.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "We are dedicated to advancing new medicines for people with cancer and that includes new methods of delivery which are more convenient for patients, physicians and healthcare systems. We look forward to collaborating with Alteogen on several assets in our portfolio with the goal of bringing new subcutaneous options to patients that can transform the way cancer care is delivered."

Dr Soon Jae Park, Chief Executive Officer of Alteogen, said: "We are excited to expand our Hybrozyme Technology by collaborating with AstraZeneca in their development of novel subcutaneous cancer medicines to meet the needs of patients."

Financial considerations
AstraZeneca will make an upfront payment to Alteogen and additional payments upon achievement of specific development, regulatory and sales-related milestones. Additionally, Alteogen will receive royalties on the sales of the commercialised products.

The transaction does not impact AstraZeneca’s financial guidance for 2025.

Notes

ALT-B4
ALT-B4 is Alteogen’s proprietary human recombinant hyaluronidase enzyme developed utilizing Hybrozyme technology. ALT-B4 can enable the large volume subcutaneous administration of drugs that are typically administered as an IV infusion. ALT-B4 does this by temporarily hydrolyzing hyaluronan in the extracellular matrix.

On March 17, 2025 AstraZeneca reported that Imfinzi (durvalumab) has been approved in the European Union (EU) as monotherapy for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy (CRT) (Press release, AstraZeneca, MAR 17, 2025, View Source [SID1234651194]).

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The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the ADRIATIC Phase III trial, which were published in The New England Journal of Medicine.

SCLC is a highly aggressive form of lung cancer, with an estimated 8,000 people treated for LS-SCLC across the five major European countries each year.1-2 LS-SCLC typically recurs and progresses rapidly, despite initial response to standard-of-care chemotherapy and radiotherapy.3-4 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients survive for five years after diagnosis.5

Suresh Senan, PhD, radiation oncologist at the Amsterdam University Medical Centers, The Netherlands, and principal investigator in the trial, said: "This approval marks a turning point for patients with limited-stage small cell lung cancer in Europe, bringing them an immunotherapy option for the first time. An unprecedented 57% of patients treated with durvalumab were still alive at three years in the ADRIATIC trial. This significant advance establishes a new benchmark in a setting where the standard of care has remained unchanged for decades."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Imfinzi has the potential to transform how limited-stage small cell lung cancer is treated as the first immunotherapy approved in Europe in this setting. As the only immunotherapy approved for both early and late-stage disease, Imfinzi is poised to become the foundation for transforming outcomes for people with small cell lung cancer."

In the trial, results showed Imfinzi reduced the risk of death by 27% versus placebo (based on an overall survival [OS] hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% for placebo.

Imfinzi also reduced the risk of disease progression or death by 24% (based on a progression-free survival [PFS] HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% for placebo.

The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed.

Imfinzi is approved in the US and several other countries in this setting based on the ADRIATIC results. Regulatory applications are currently under review in Japan and several other countries for this indication. Imfinzi is also approved in combination with chemotherapy for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial.

Notes

Small cell lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6-7 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% of cases classified as SCLC.8

LS-SCLC (Stage I-III) accounts for approximately 30% of SCLC diagnoses and is classified when the disease is generally only in one lung or one side of the chest.9 The prognosis for patients with LS-SCLC remains poor despite curative-intent treatment with standard-of-care concurrent CRT (cCRT).10

ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months.

The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to its indications in SCLC, Imfinzi is also the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after CRT. Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC; and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours.

On March 17, 2025 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company developing a potentially first-in-class and best-in-class WEE1 inhibitor for patients with ovarian cancer and other tumor types, reported updated clinical data from Part 1b of the ongoing DENALI clinical trial of azenosertib in patients with PROC in an oral presentation at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer (Press release, Zentalis Pharmaceuticals, MAR 17, 2025, View Source [SID1234651193]).

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DENALI Part 1b is a Phase 2 single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose (once daily, five days on, two days off, or the "intermittent schedule") in patients with PROC (n=102).

As of the January 13, 2025 data cutoff, patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib) demonstrated an ORR of 34.9% (15/43; 95% CI: 21.0 – 50.9). In the intent-to-treat patients with Cyclin E1+ PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 – 46.3), and an mDOR of 6.3 months (95% CI: 2.7 – not estimable). The mDOR is subject to change since there were patients with ongoing responses as of the cutoff date.

The presentation also demonstrates Cyclin E1 protein overexpression, regardless of CCNE1 gene amplification, as a sensitive and specific predictive biomarker that can be used to identify patients who could potentially derive benefit from azenosertib. Zentalis estimates that about half of PROC patients overexpress Cyclin E1 based on its proprietary immunohistochemistry cutoff.

As of the January 13, 2025 data cutoff, the safety and tolerability profile was consistent with the safety and tolerability profile from the Company’s January 29, 2025 investor event, which included data based off a cutoff date of December 2, 2024, with no new safety findings. Gastrointestinal toxicities and fatigue were found to be the most common treatment-related adverse events.

"The presentation of the updated DENALI Part 1b data at the SGO Annual Meeting supports our continued development of azenosertib," said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. "The clear anti-tumor activity and durable response observed highlights the potential of azenosertib to become an important treatment option for patients with Cyclin E1+ PROC. We are proud to have shared these data with many of the world’s leading gynecologic oncologists at SGO as part of our continued commitment to patients living with PROC."

"Platinum-resistant ovarian cancer is one of the most challenging types of ovarian cancer to treat. Tumors overexpressing Cyclin E1 protein exhibit poorer outcomes after standard of care chemotherapy regimens," said Fiona Simpkins, M.D., Director of Clinical & Translational Gynecologic Oncology Research at the University of Pennsylvania, and lead principal investigator in the DENALI study. "Developing new therapies for this subset of ovarian cancer patients is urgently needed. DENALI Part 1b results are exciting as they show that the WEE1 inhibitor, azenosertib, is active in a Cyclin E1 biomarker selective population potentially addressing a clinical unmet need."

The Company is on track to initiate enrollment of DENALI Part 2 in the first half of 2025 and expects to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. Zentalis plans to treat the same patient population in a Phase 3 randomized confirmatory study, subject to FDA review, which the Company plans to enroll concurrently with DENALI Part 2b.

Tomorrow, the Company will also present preclinical data of azenosertib during a poster presentation at the SGO Annual Meeting. The poster data highlights synergistic effects and significantly improved tumor growth inhibition in in vitro and in vivo preclinical models using a combination of azenosertib and microtubule inhibitor-based ADCs. Together with the previous data that azenosertib synergized with TOPO1 inhibitor based ADCs, these results indicate that azenosertib could be used as a generalizable combination partner with ADCs for improving responses in patients with advanced solid tumors.

The oral presentation and poster can be accessed through the "Publications" section of the Zentalis website.

About Azenosertib

Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.