On June 2, 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 and WNT pathway inhibitor—today announced that the first patient has been enrolled in its new Phase 2 clinical trial protocol of stenoparib for the treatment of advanced, platinum-resistant or platinum-ineligible ovarian cancer (Press release, Allarity Therapeutics, JUN 2, 2025, https://allarity.com/press-release/allarity-therapeutics-announces-first-patient-enrolled-in-new-phase-2-clinical-trial-protocol-of-stenoparib-in-advanced-ovarian-cancer/ [SID1234653633]).

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The newly launched protocol will accelerate the clinical development of stenoparib and its drug-specific Drug Response Predictor (DRP) companion diagnostic (CDx) toward potential FDA approval. It builds on encouraging data from Allarity’s earlier and still ongoing Phase 2 study, which demonstrated that patients on twice-daily stenoparib showed durable clinical benefit and that stenoparib was well tolerated. Two patients remain on treatment and continue to derive benefit after more than 20 months. Reflecting the compelling and durable clinical responses observed in platinum-resistant patients to date, the new trial protocol specifically focuses on evaluating stenoparib in patients with advanced, recurrent, platinum-resistant, or platinum-ineligible ovarian cancer—patients for whom current treatment options are extremely limited and typically involve additional chemotherapy, which is associated with well-documented side effects.

"With the enrollment of the first patient, we are fulfilling our promise to accelerate stenoparib’s clinical development as a potentially safer, more effective alternative to chemotherapy for women with advanced, recurrent ovarian cancer," said Thomas Jensen, Chief Executive Officer of Allarity Therapeutics. "This new protocol reflects critical input from leading gynecologic oncologists, and allows us to solidify the importance of DRP for patients who are most likely to receive clinical benefit from stenoparib. This study also allows us to confirm and extend our current findings that show clinical benefit from twice daily dosing."

In addition to assessing overall efficacy and safety, the new trial protocol is designed to further advance the Company’s understanding of stenoparib’s modulation of the WNT signaling pathway—a key driver of disease progression in ovarian and other cancers. The Company is actively pursuing ways to deepen its insights into the therapeutic importance of this WNT-modulating activity and how this, in addition to a cleaner safety profile, distinguishes stenoparib from first-generation PARP inhibitors.

Building on the clinical benefit of the current dosing schedule, this updated study design also includes an additional dosing level to explore the optimal dose for enhancing clinical benefit, aligning Allarity with the FDA’s Project Optimus initiative to inform the start of pivotal registration trials.

The trial is expected to generate significant clinical data by late summer 2026. Allarity plans to pursue multiple advantaged regulatory pathways to expedite potential approval of both stenoparib and its DRP companion diagnostic (CDx).

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.

About the Drug Response Predictor – DRP Companion Diagnostic
Allarity uses its drug-specific DRP to select those patients who, by the gene expression signature of their cancer, may have a high likelihood of benefiting from a specific drug. By screening patients before treatment, and only treating those patients with a sufficiently high, drug-specific DRP score, the therapeutic benefit rate may be enhanced. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including transcriptomic information from cell lines, combined with clinical tumor biology filters and prior clinical trial outcomes. DRP is based on messenger RNA expression profiles from patient biopsies. The DRP platform has shown an ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients across dozens of clinical studies (both retrospective and prospective). The DRP platform, which may be useful in all cancer types and is patented for dozens of anti-cancer drugs, has been extensively published in the peer-reviewed literature.

On June 2, 2025 PharmaMar (MSE:PHM) reported positive results from the Phase 3 IMforte study of Zepzelca (lurbinectedin) in combination with atezolizumab (Tecentriq) as a first-line maintenance treatment for people with extensive-stage small cell lung cancer (ES-SCLC), following induction therapy with carboplatin, etoposide and atezolizumab (Press release, PharmaMar, JUN 2, 2025, View Source [SID1234653632]). The study met both primary endpoints, demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to atezolizumab alone.

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IMforte is the first global Phase 3 trial to demonstrate clinically meaningful PFS and OS benefits in the first-line maintenance setting for ES-SCLC and supports maintenance therapy with lurbinectedin plus atezolizumab as a new standard of care for patients. The data were presented today in an oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago and published simultaneously in The Lancet. Data from the trial served as the basis for the supplemental New Drug Application (sNDA) submission to the FDA by Jazz Pharmaceuticals, as well as for the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) by PharmaMar.

Following induction therapy with carboplatin, etoposide and atezolizumab, patients who did not have disease progression were randomized to receive lurbinectedin plus atezolizumab or atezolizumab alone. From the point of randomization, the median PFS was 5.4 months for the lurbinectedin plus atezolizumab combination versus 2.1 months for atezolizumab alone (stratified HR = 0.54, 95% CI: 0.43–0.67; p < 0.0001), and median OS was 13.2 months versus 10.6 months (stratified hazard ratio [HR] = 0.73; 95% CI: 0.57–0.95; p = 0.0174). The combination reduced the risk of disease progression or death by 46% and the risk of death by 27% compared to atezolizumab alone. The lurbinectedin plus atezolizumab combination had no new or unexpected safety signals.

"Small cell lung cancer is an aggressive and devastating disease; at the time of diagnosis, the large majority of patients have already progressed to extensive-stage disease and only one out of five survive longer than two years," said Luis Paz-Ares, M.D., Ph.D., head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, and the IMforte trial principal investigator. "The IMforte results are very encouraging showing a potentially practice-changing option that could improve survival for patients with a very high unmet need."

"Upon approval, patients will have access to lurbinectedin earlier in the treatment paradigm, where there’s potential to increase duration of response in a broader patient population, delaying disease progression and extending survival," said Javier Jiménez Jiménez, Chief Medical Officer of PharmaMar.

Each year, approximately 63,000 to 72,000 new cases of small cell lung cancer (SCLC) are reported in Europe. Most of these patients are diagnosed with extensive stage disease, which is aggressive and often difficult to treat, with poor prognosis.

On June 2, 2025 mAbxience, a Fresenius Kabi majority-owned group with partial ownership from Insud Pharma, and Corapharm reported a new strategic licensing agreement to develop and commercialize a biosimilar candidate in Southeast Europe (Press release, mAbxience, JUN 2, 2025, View Source [SID1234653631]).

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Under the terms of the agreement, mAbxience will hold the marketing authorization for the biosimilar candidate in Croatia and Slovenia, while Corapharm will assume this role across Serbia, Bosnia and Herzegovina, North Macedonia, Montenegro, Kosovo, and Albania. Corapharm will lead commercialization efforts throughout these territories, with mAbxience overseeing the product’s development and manufacturing at its state-of-the-art facilities.

"We are excited to partner with Corapharm to bring this biosimilar candidate to patients across Southeast Europe. Our collaboration reflects mAbxience’s commitment to delivering high-quality, accessible therapies across various geographies," said José Ramón Millán, Global Partnering & Portfolio Director at mAbxience.

"Building on our successful track record in the pharmaceutical industry, we look forward to working with mAbxience to improve patient outcomes and expand access to critical treatments in these countries," noted Mr. Miroslav Roca, CEO of Corapharm d.o.o.. "Together, we remain dedicated to enhancing patient care and addressing the rising costs of biologic therapies."

This agreement marks another milestone in mAbxience’s strategy to provide affordable, life-saving therapies worldwide. Both mAbxience and Corapharm expect that this partnership will enhance patient access to advanced treatments, while also helping healthcare systems manage the rising costs of biologic therapies.

On June 2, 2025 Amgen (NASDAQ:AMGN) reported new interim results from the global Phase 3 DeLLphi-304 trial showing IMDELLTRA (tarlatamab-dlle) reduced the risk of death by 40% and significantly extended median overall survival (OS) by more than five months compared to standard-of-care (SOC) chemotherapy in patients with small cell lung cancer (SCLC) who progressed on or after one line of platinum-based chemotherapy (median OS: 13.6 vs 8.3 months; hazard ratio [HR], 0.60; 95% confidence interval [CI]: 0.47, 0.77; P < 0.001) (Press release, Amgen, JUN 2, 2025, View Source [SID1234653630]). The results will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (LBA8008) and have been published in The New England Journal of Medicine.

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"Small cell lung cancer is an extraordinarily aggressive and difficult-to-treat disease, and those living with SCLC often experience limited benefit with first line treatment," said Jay Bradner, M.D., executive vice president, Research and Development, at Amgen. "These data underscore IMDELLTRA’s potential to transform patient outcomes and the small cell lung cancer treatment paradigm."

At the planned interim analysis, DeLLphi-304 met its primary OS endpoint and key secondary progression-free survival (PFS) endpoint. Additionally, IMDELLTRA significantly improved patient-reported outcomes (PRO) for cancer-related symptoms of dyspnea and cough compared to the control arm.

"The data from DeLLphi-304 mark a major milestone for people with relapsed small cell lung cancer. Tarlatamab is associated with significant improvements in both overall and progression-free survival over standard chemotherapy in patients with recurrent or progressive disease," said Charles Rudin, M.D., Ph.D., deputy director, Memorial Sloan Kettering Cancer Center. "This study also provides confirmatory data on management of potential toxicities associated with bispecific T-cell engager therapies in a large patient cohort, which is crucial to continuing to improve the experience of patients treated with these medicines."

At a median follow-up of 11.2 months for IMDELLTRA and 11.7 months for the control arm, data from the global Phase 3 DeLLphi-304 clinical trial showed a median OS of 13.6 months with IMDELLTRA compared to 8.3 months with local SOC chemotherapy (HR, 0.60; 95% CI: 0.47, 0.77; P < 0.001). Median PFS was statistically significantly improved for IMDELLTRA compared to local SOC chemotherapy (median PFS: 4.2 vs 3.7 months; HR, 0.71; 95% CI: 0.59, 0.86; P < 0.001).

The safety profile for IMDELLTRA in DeLLphi-304 was consistent with its known profile. In DeLLphi-304, lower rates of grade 3 or higher treatment-related adverse events (TRAEs) occurred with IMDELLTRA versus the control arm (27% vs 62%) and discontinuations due to TRAEs were lower with IMDELLTRA compared to the control arm (3% vs 6%). The most common grade 3 or greater TRAEs were neutropenia (4%) and lymphopenia (4%) with IMDELLTRA and anemia (28%) and neutropenia (22%) with local SOC chemotherapy. Cytokine release syndrome (CRS) with IMDELLTRA primarily occurred after receipt of one of the first two doses and was primarily low grade (42% Grade 1; 13% Grade 2; 1% Grade 3) and manageable. No Grade 4 or Grade 5 CRS events were reported. CRS profiles following the first two doses of IMDELLTRA, including incidence, severity, outcome, time to intervention and time to resolution, were similar among patients who were monitored for 6 to 8 hours (n=43) and those who were monitored for 48 hours (n=209).

DeLLphi-304 is a global Phase 3, randomized, controlled, open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients living with SCLC who progressed on or after a single line of platinum-based chemotherapy.1 Five hundred and nine patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except Japan; lurbinectedin in the U.S., Canada, Australia, Singapore, Korea; and amrubicin in Japan).1,2 The primary outcome measure of the trial is OS.1 Key secondary outcome measures include PFS and PROs including disease-related symptoms, physical function and quality of life.1 DeLLphi-304 is intended to serve as the confirmatory trial for IMDELLTRA’s accelerated approval for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

About IMDELLTRA (tarlatamab-dlle)
IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.3,4 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.5,6

IMDELLTRA (tarlatamab-dlle) U.S. Indication
IMDELLTRA (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5-10% five-year relative survival rate across all stages combined.7 SCLC comprises about 15% of the more than 2.4 million patients diagnosed with lung cancer worldwide each year.8-10 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.9

About Tarlatamab Clinical Trials
Amgen’s robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens, including in both earlier stages of SCLC and earlier lines of treatment.

Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 study comparing tarlatamab monotherapy with standard-of-care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 study comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC; DeLLphi-310, a Phase 1b study of tarlatamab in combination with YL201 with or without anti-programmed death ligand 1 (PD-L1) in patients with ES-SCLC; and DeLLphi-312, a Phase 3 study evaluating tarlatamab as an induction and maintenance therapy in first-line treatment of ES-SCLC in combination with carboplatin, etoposide, and durvalumab.

On June 2, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the presentation of the uTRACT Registry study design at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, UroGen Pharma, JUN 2, 2025, View Source [SID1234653627]). The uTRACT Registry is a single-arm, multicenter, prospective and retrospective study evaluating the real-world use of JELMYTO (mitomycin) for pyelocalyceal solution for the treatment of adult patients with low-grade upper tract urothelial carcinoma (LG-UTUC) across the United States.

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"By capturing these real-world insights, the uTRACT Registry will inform best practices in the management of LG-UTUC," said Mark Schoenberg, Chief Medical Officer, UroGen. "This robust data set aims to support the ongoing clinical utility of JELMYTO in managing LG-UTUC, offering new insights into treatment patterns, long-term outcomes, and patient safety in real-world settings."

As of May 2025, the uTRACT Registry (NCT05874921) has enrolled 274 participants across 22 clinical sites nationwide, with a target enrollment of approximately 400 patients. Of these, about 340 are expected to have LG-UTUC, the population for which JELMYTO is FDA-approved. The study is designed to collect comprehensive data over a three-year period. This includes patient history and baseline disease characteristics prior to initiating treatment with JELMYTO, as well as details on the mode of administration, dosing regimens, surveillance endoscopy findings, and imaging results. Investigators will assess key clinical outcomes such as the presence of no evidence of disease at three months post-treatment, duration of response, recurrence-free survival, time to recurrence or progression, and adverse events.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel approved for the treatment of adult patients with LG-UTUC. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through a nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

About Upper Tract Urothelial Cancer

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as UTUC. In the U.S., there are approximately 6,000 – 7,000 new or recurrent LG-UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often have multiple comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). Treatment with endoscopic surgery can be associated with a high rate of recurrence and relapse.