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Nuvalent Announces Timing of Pivotal Data for TKI Pre-treated Patients with Advanced ROS1-positive NSCLC from ARROS-1 Clinical Trial of Zidesamtinib

On June 23, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that the company will host a webcast and conference call on Tuesday, June 24, 2025 at 8:00 a.m. ET, to discuss pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI pre-treated patients with advanced ROS1-positive non-small cell lung cancer from the global ARROS-1 Phase 1/2 clinical trial (Press release, Nuvalent, JUN 23, 2025, View Source [SID1234654074]).

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Webcast and Conference Call Information

To access the call, please dial +1 (800) 836-8184 (domestic) or +1 (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined to the Nuvalent call.

Accompanying slides and a live video webcast will be available in the Investors section of the Nuvalent website at https://investors.nuvalent.com/events. A replay and accompanying slides will be archived on the Nuvalent website for 30 days.

About Zidesamtinib and the ARROS-1 Phase 1/2 Clinical Trial

Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC.

Zidesamtinib is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. The completed Phase 1 portion enrolled ROS1-positive NSCLC patients who previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors who had been previously treated. The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of zidesamtinib, with additional objectives including determination of the recommended Phase 2 dose, characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity. The ongoing global, single arm, open label Phase 2 portion is designed with registrational intent for TKI-naïve and TKI pre-treated patients with ROS1-positive NSCLC.

Hoth Therapeutics to host KOL Event Spotlighting HT-001, Novel Therapy

On June 23, 2025 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company developing innovative therapies, reported that they will host a virtual Key Opinion Leader (KOL) event on Tuesday, June 24, 2025, at 3:30PM EST (Press release, Hoth Therapeutics, JUN 23, 2025, View Source [SID1234654070]). Access/join the event through the following link: View Source

Hoth Therapeutics will host a Key Opinion Leader (KOL) event on June 24, 2025, at 3:30PM EST to highlight recent clinical progress with HT-001, a novel topical therapeutic developed to address EGFR inhibitor-induced skin toxicities in cancer patients. This event will feature insights from derm-oncology and dermatology specialists Jonathan Hale Zippin M.D., Ph.D., and Adam Friedman M.D., F.A.A.D., who will present interim results from the ongoing Phase 2 trial and discuss how HT-001 could redefine supportive care standards for oncology patients.

Datroway approved in the US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer

On June 23, 2025 Astrazeneca reported Datroway (datopotamab deruxtecan or Dato-DXd) has been approved in the US for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy (Press release, AstraZeneca, JUN 23, 2025, View Source [SID1234654067]).

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

The approval follows Priority Review and Breakthrough Therapy Designation by the Food and Drug Administration (FDA) based on results from a subgroup analysis of the TROPION-Lung05 Phase II trial and supported by data from the TROPION-Lung01 Phase III trial.

Jacob Sands, MD, Medical Oncology, Dana-Farber Cancer Institute and investigator in both trials, said: "Addressing disease progression in patients with advanced EGFR-mutated lung cancer after prior targeted therapy and chemotherapy is very challenging with limited later-line treatment options available. The US approval of datopotamab deruxtecan introduces a novel and needed treatment option to patients with advanced disease."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "This first approval of Datroway in lung cancer provides a much-needed option to patients with advanced EGFR-mutated lung cancer whose disease has become resistant to past treatments, regardless of the driving mutation. We have long supported patients with EGFR-mutated lung cancer and are proud to bring another innovative treatment option to this community."

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc, said: "With today’s accelerated approval, Datroway is now the first TROP2-directed medicine available for certain patients in the US living with lung cancer. We remain committed to our extensive clinical development programme to further identify where Datroway may be used in other types of lung and breast cancer."

Andrea E. Ferris, President and CEO, LUNGevity, said: "For people with advanced EGFR-mutated non-small cell lung cancer whose disease progresses on initial treatments, additional options are limited. Today’s approval of Datroway offers a new treatment option for patients whose disease has progressed following treatment with an EGFR-directed therapy and chemotherapy."

In TROPION-Lung05 and TROPION-Lung01, Datroway demonstrated a confirmed ORR of 45% (95% confidence interval [CI]: 35-54) in patients with previously treated locally advanced or metastatic EGFR-mutated NSCLC (n=114) as assessed by blinded independent central review (BICR). Complete responses were seen in 4.4% of patients and partial responses were seen in 40% of patients. The median DoR was 6.5 months (95% CI: 4.2-8.4).

The safety profile of Datroway was evaluated in a pooled analysis of 125 patients in the TROPION-Lung05, TROPION-Lung01 and TROPION-PanTumor01 trials. The safety profile observed across these trials was consistent with the known profile of this medicine with no new safety concerns identified.

Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

AstraZeneca and Daiichi Sankyo are evaluating Datroway alone and with Tagrisso (osimertinib) in other advanced or metastatic EGFR-mutated NSCLC settings in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

Financial considerations
Following approval in the US, an amount of $45 million is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the locally advanced or metastatic EGFR-mutated NSCLC indication. Sales of Datroway in the US are recognized by Daiichi Sankyo. For further details on the financial arrangements, please consult the collaboration agreement from July 2020.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 87% of cases.2 Approximately 10 to 15% of patients with NSCLC in the US and Europe, and 30 to 40% of patients in Asia have an EGFR mutation.3,4 The majority of EGFR mutations occur in tumours of nonsquamous histology.5 TROP2 is a protein broadly expressed in the majority of NSCLC tumours.6

For patients with tumours that have an EGFR mutation, the established 1st-line treatment in the metastatic setting includes EGFR-directed therapy with or without platinum-based chemotherapy.7 While these therapies have improved outcomes in earlier lines of treatment, most patients eventually experience disease progression and receive subsequent therapies.8-11

TROPION-Lung05
TROPION-Lung05 is a global, multicentre, single-arm, open-label Phase II trial evaluating the efficacy and safety of Datroway in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one EGFR-directed therapy and platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumours with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial.

The primary endpoint of TROPION-Lung05 is ORR as assessed by BICR. Secondary efficacy endpoints include DoR, disease control rate (DCR), clinical benefit rate, PFS, time to response (TTR), OS and safety. TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information, visit ClinicalTrials.gov.

Primary results from TROPION-Lung05 were published in the Journal of Clinical Oncology in January 2025.

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of Datroway versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled 590 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

Primary results from TROPION-Lung01, as presented at the ESMO (Free ESMO Whitepaper) 2023 Congress, showed Datroway demonstrated a statistically significant improvement in PFS over docetaxel. OS results were presented at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology in September 2024.

TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of Datroway in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with NSCLC to assess the safety and tolerability of Datroway to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 enrolled several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration resistant prostate and oesophageal cancer.

Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated. TROPION-PanTumor01 enrolled 890 patients in Asia and North America. For more information, visit ClinicalTrials.gov.

Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US 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 programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised 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 is approved in more than 30 countries 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 is available in the US under accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway is approved in Russia for the same population.

Datroway clinical development programme
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and HR-positive, HER2-negative breast cancer. The programme includes eight Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating Datroway as a monotherapy and in combination with other anticancer treatments in various settings.

Actinium Highlights Expanded Data Set for ATNM-400 in Prostate Cancer Demonstrating Superior Efficacy to Enzalutamide and Ability to Overcome Resistance to ARPI Therapy and PSMA-Ac-225/Lu-177 Labelled Radiotherapy at the Society of Nuclear Medicine & Molecular Imaging Annual Meeting

On June 23, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported new preclinical data from its first-in-class, non-PSMA targeting radiotherapy prostate cancer candidate ATNM-400, that leverages the potent alpha-particle emitter Actinium-225 (Ac-225) isotope, at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) annual meeting being held June 21st – 24th, 2025, in New Orleans, Louisiana (Press release, Actinium Pharmaceuticals, JUN 23, 2025, View Source [SID1234654066]). The data presented at SNMMI showed ATNM-400 has superior potency compared Xtandi (enzalutamide) and is highly efficacious in Xtandi resistant prostate models. Xtandi is an androgen receptor inhibitor (ARPI) therapy developed and marketed by Astellas and Pfizer that is approved for three stages of prostate cancer and generated sales of $5.9 billion in 2024. Actinium also presented additional new data showing ATNM-400 is more efficacious than PSMA-617 labeled with both Lutetium-177 (Lu-177) and Ac-225 and that ATNM-400 also overcomes resistance to Pluvicto (Lu-177-PSMA-617). Pluvicto is developed and marketed by Novartis and generated sales of $1.4 billion in 2024. ATNM-400 represents a transformational therapeutic candidate being developed to overcome limitations of current prostate cancer therapies such as Xtandi and Pluvicto and improve outcomes over what is currently achievable. Key data and highlights from the ATNM-400 SNMMI presentation include:

ATNM-400 Target Expression Profile and Disease Biology

The ATNM-400 target is implicated in prostate cancer disease biology and contributes directly to disease progression, with expression correlating with shorter time to castration resistance and poorer survival in castrate resistant prostate cancer (CRPC) patients making it differentiated from PSMA, which serves primarily as a surface marker

The target for ATNM-400 is also reported to be elevated in prostate cancer patients who develop resistance to the ARPI therapy Xtandi

ATNM-400 shows consistent tumor uptake, rapid clearance from the blood and clearance from vital organs including intestines, liver, and kidneys

Target expression is retained post Pluvicto treatment in prostate cancer models
ATNM-400 Compared to Xtandi (enzalutamide)

ATNM-400 exhibited potent killing of all Xtandi resistant prostate cancer cells that remained following treatment with Xtandi, with Xtandi only killing 50% of the resistant prostate cancer cells

ATNM-400 monotherapy and in combination with Xtandi had superior anti-tumor efficacy in vivo compared to Xtandi alone in a prostate cancer model; all treatments were well-tolerated with no change in body weight

ATNM-400 inhibited tumor growth of Xtandi resistant tumors whereas re-treatment with Pluvicto or additional enzalutamide did not

ATNM-400 Compared to PSMA targeted Radiotherapy

ATNM-400 was more potent than both Pluvicto (177Lu-PSMA-617) and 225Ac-PSMA-617 in prostate cancer cell killing

At therapeutically relevant doses, ATNM-400 exhibited more efficacious tumor growth inhibition compared to both Pluvicto and 225Ac-PSMA-617 in prostate cancer in vivo model

As previously reported, ATNM-400 was able to overcome Pluvicto resistance, halting tumor growth in prostate cancer tumors that failed Pluvicto therapy and producing potent tumor cell killing

Sandesh Seth, Actinium’s Chairman and CEO, said, "We are committed to advancing ATNM-400 to address the high unmet needs that remain in prostate cancer. These new data presented at SNMMI demonstrate the therapeutic potential of ATNM-400 as both a monotherapy and in combination with both androgen receptor inhibitors and PSMA radiotherapy, two leading prostate cancer treatment modalities. With ATNM-400’s target being a disease-driving protein involved in tumor progression and therapeutic resistance combined with the potency and precision of the Ac-225 isotope payload, we believe ATNM-400 has a transformational profile rooted in prostate cancer disease biology, which is strongly supported by our data. We are thrilled to highlight ATNM-400’s first-in-class data at SNMMI and highly encouraged by the strong interest from KOL’s across the prostate cancer and nuclear medicine communities. As Actinium continues to advance our efforts with novel targeted radiotherapies, ATNM-400 is the ideal cornerstone of our emerging solid tumor pipeline."

The ATNM-400 SNMII presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: First-in-class antibody radioconjugate ATNM-400 exhibits potent anti-tumor activity and overcomes resistance to enzalutamide and 177Lu-PSMA-617 in prostate cancer models

About ATNM-400

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC), contributes directly to disease progression and poorer survival outcomes, and continues to be expressed at a high level even after androgen receptor inhibitor and Pluvicto treatment. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal irreversible double-stranded DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Vertex and Ono Pharmaceutical Announce Strategic Agreement to Develop and Commercialize Povetacicept in Japan and South Korea

On June 23, 2025 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and Ono Pharmaceutical Co., Ltd. (OTCMKTS: OPHLY) reported an exclusive collaboration and license agreement for the development and commercialization of Vertex’s povetacicept in Japan and South Korea (Press release, Vertex Pharmaceuticals, JUN 23, 2025, View Source [SID1234654064]). Povetacicept is a recombinant fusion protein therapeutic and dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines with best-in-class potential being studied for the treatment of immunoglobulin A nephropathy (IgAN), primary membranous nephropathy (pMN) and other B cell-mediated diseases.

Under the terms of the agreement, Vertex will receive an upfront payment, as well as certain regulatory and commercial milestone payments and tiered royalties. Ono will utilize its extensive development expertise to help advance Vertex’s clinical trials for povetacicept and will be responsible for obtaining marketing authorizations in Japan and South Korea. Following approval, Ono will be solely responsible for commercializing povetacicept in these regions. The agreement includes povetacicept for both IgAN and pMN, with the potential to add other indications.

"Ono is a proven leader in Japan and South Korea, bringing established local relationships, infrastructure and nephrology expertise that make them a perfect partner for Vertex as we look to deliver povetacicept to the thousands of potential patients in these countries," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. "We are very pleased to partner with Ono and look forward to close collaboration as we continue to advance this potentially best-in-class treatment for IgAN, pMN and other serious B cell-mediated diseases."

"Vertex has a strong track record of developing innovative therapies for serious diseases. Through this strategic partnership, we can strengthen our late-stage pipeline in the immunology field, which is a key focus area for Ono," said Toichi Takino, Representative Director, President and Chief Operating Officer of Ono. "We look forward to collaborating with Vertex to provide this new therapeutic option for patients with IgAN and other autoimmune diseases in Japan and South Korea, and to maximize the value of this treatment."

About Povetacicept

Povetacicept is a recombinant fusion protein therapeutic and a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and calcium modulator ligand interactor) domain, povetacicept has higher binding affinity and greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and has demonstrated potential best-in-class efficacy in a clinical trial in patients with IgA nephropathy and primary membranous nephropathy. Povetacicept is also in development for multiple serious B cell-mediated diseases including other autoimmune kidney diseases and autoimmune cytopenias.

About IgA Nephropathy (IgAN)

IgAN is a serious, progressive, life-threatening, B cell-mediated chronic kidney disease that is the most common cause of primary (idiopathic) glomerulonephritis, affecting approximately 300,000 people in the United States and Europe. It is estimated that there are approximately 33,000 diagnosed patients in Japan. IgAN results from deposition of circulating immune complexes consisting of immunoglobulins and galactose-deficient immunoglobulin A (Gd-IgA1) in the renal glomerular mesangium, triggering kidney injury and fibrosis. Up to 72% of adult IgAN patients progress to end-stage renal disease within 20 years. There are no approved therapies that specifically target the underlying cause of IgAN.

About Primary Membranous Nephropathy (pMN)

Primary membranous nephropathy is a serious, progressive, life-threatening B cell-mediated chronic kidney disease affecting people worldwide, with approximately 150,000 people diagnosed in the U.S. and Europe. It is estimated that there are approximately 6,000 diagnosed patients with pMN in Japan. pMN is a rare glomerular disease that occurs when the body generates an abnormal immune response, including autoantibodies, against proteins that are part of the kidney. Autoantibodies trigger damage and inflammation, especially within the glomeruli (the parts of the kidney that filter blood), impairing the kidneys’ ability to properly filter waste and fluid, eventually causing progressive loss of kidney function. There are no approved therapies that specifically target the underlying cause of pMN.

About RAINIER

RAINIER is a global Phase 3 pivotal trial of povetacicept 80 mg vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating urine protein to creatinine ratio (UPCR) for the povetacicept arm versus placebo after a certain number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total eGFR slope through Week 104.

The Phase 3 clinical trial is underway in multiple regions, including the U.S., EU and Asia. Specifically, Japanese and South Korean regulatory authorities have approved the Clinical Trial Application (CTA) for RAINIER, where the Phase 3 trial is underway.

About RUBY-3

RUBY-3 is an ongoing, multiple ascending dose, multi-cohort, open label, Phase 1/2 basket study of povetacicept in autoimmune glomerulonephritis, including IgAN, primary membranous nephropathy, lupus nephritis and ANCA-associated vasculitis with glomerulonephritis where povetacicept is being administered subcutaneously for up to 104 weeks.