Adagrasib

ATNM-400 demonstrated activity across EGFR-, KRAS- and ALK-driven lung cancer models, supporting mutation-agnostic development as monotherapy and in combination with established treatments In colorectal cancer, adding ATNM-400 to standard therapy increased tumor growth inhibition to 72% from 25% for oxaliplatin and bevacizumab in a poorly responsive model with moderate target expression In ovarian cancer, ATNM-400 achieved 93% tumor growth inhibition as monotherapy and retained activity following bevacizumab failure Three presentations expand the preclinical foundation for ATNM-400 as a potential pan-tumor treatment, complementing ongoing clinical development in prostate cancer NEW YORK, Oct. 20, 2026 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) (Actinium or the Company), a pioneer in differentiated targeted radiotherapies with the potential to transform cancer treatment, today announced new preclinical results demonstrating the broad antitumor potential of ATNM-400 across non-small cell lung cancer (NSCLC), colorectal cancer and ovarian cancer models. The findings were presented in an oral presentation and two e-posters at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM), October 17–21, 2026, in Vienna, Austria. ATNM-400 is the Company's first-in-class Actinium-225 (²²⁵Ac) antibody radioconjugate targeting HER3, a tumor-associated antigen implicated in cancer-cell survival and treatment resistance. By delivering high-energy alpha-particle radiation to HER3-expressing tumor cells, ATNM-400 is designed to induce DNA double-strand breaks through a mechanism distinct from conventional pathway inhibition. The EANM results demonstrate activity across molecularly diverse tumors and treatment-resistant disease, supporting development as both a standalone therapy and a combination partner for established treatments. The studies broaden ATNM-400's preclinical evidence beyond previously reported prostate and breast cancer findings and extend its lung cancer program across multiple oncogenic drivers. Together with the Company's ongoing clinical development in metastatic castration-resistant prostate cancer (mCRPC), these results support a strategy to advance ATNM-400 across multiple large solid tumor indications. Sandesh Seth, Actinium's Chairman and CEO, said, "These results strengthen our conviction in ATNM-400's pan-tumor potential and our opportunity to expand targeted radiotherapy across major solid tumor indications. In lung cancer, activity across EGFR-, KRAS- and ALK-driven models supports an approach that could reach patients beyond a single mutation-defined population. In colorectal cancer, ATNM-400 substantially improved tumor control when added to a standard regimen with limited activity, while in ovarian cancer it demonstrated strong single-agent activity, including after bevacizumab failure. This breadth of activity supports our vision for ATNM-400 as a potential treatment backbone, both on its own and alongside established therapies, for patients whose cancers are inadequately served by current options." Adeela Kamal, Ph.D., Actinium's Chief Scientific Officer, added, "HER3 provides a compelling biological link across these cancers through its role in tumor-cell survival and treatment resistance. ATNM-400 uses this target to deliver the potent DNA-damaging effects of Actinium-225, with activity that is not dependent on inhibiting a specific oncogenic driver. The activity across distinct lung cancer subtypes, improved responses to standard therapy in colorectal cancer, and retained activity after bevacizumab failure in ovarian cancer strengthen the scientific rationale for this approach. These findings support further development of ATNM-400 across HER3-expressing solid tumors, with combinations selected to build on its single-agent activity." Highlights from the EANM 2026 Presentations Non-Small Cell Lung Cancer | Oral Presentation EPS-149 ATNM-400 demonstrated antitumor activity across EGFR-mutant, KRAS G12C-mutant and ALK-rearranged NSCLC models, supporting a HER3-directed approach with potential beyond any single oncogenic driver. In the KRAS G12C-mutant NCI-H358 model, ATNM-400 monotherapy achieved 81% tumor growth inhibition (TGI), compared with 38% for adagrasib and 29% for the HER3-directed antibody-drug conjugate patritumab deruxtecan. Combining ATNM-400 with adagrasib increased TGI to 105%, consistent with tumor regression. These findings support both single-agent activity and the potential to deepen responses to KRAS-targeted therapy. In the ALK-rearranged NCI-H3122 model, ATNM-400 plus crizotinib achieved 97% TGI, compared with 50% for ATNM-400, 55% for crizotinib and 26% for patritumab deruxtecan alone. ATNM-400-containing regimens were well tolerated and extended survival relative to controls and the HER3-directed antibody-drug conjugate. In the EGFR-mutant NCI-H1975 model, ATNM-400 plus pemetrexed and cisplatin achieved 86% TGI, compared with 52% for amivantamab plus chemotherapy and 48% for amivantamab plus lazertinib. ATNM-400 monotherapy achieved 63% TGI. The ATNM-400 and chemotherapy combination also prolonged survival during the study period. Colorectal Cancer | e-Poster EP-0163 ATNM-400 demonstrated combination activity in colorectal cancer models spanning moderate-to-high HER3 expression, including tumors with limited sensitivity to standard therapy. In the HCT15 model with moderate HER3 expression, ATNM-400 plus oxaliplatin and bevacizumab achieved 72% TGI, compared with 25% for oxaliplatin and bevacizumab and 27% for ATNM-400 alone at the corresponding dose. The combination extended survival, supporting its potential to improve tumor control where standard therapy has limited activity. In the SW620 model with high HER3 expression, ATNM-400 plus bevacizumab achieved 88% TGI, comparable to 85% for oxaliplatin plus bevacizumab, while ATNM-400 monotherapy achieved 57% TGI. Survival with ATNM-400 plus bevacizumab was also comparable to the chemotherapy-containing regimen, supporting further evaluation of a combination that omits oxaliplatin. Ovarian Cancer | e-Poster EP-0176 ATNM-400 demonstrated strong single-agent activity in ovarian cancer, including after bevacizumab failure, with additional survival findings in an immunocompetent model of disseminated disease. In the OVCAR-5 model, ATNM-400 monotherapy achieved 93% TGI, compared with 54% for bevacizumab. The combination achieved 85% TGI without additional benefit over ATNM-400 alone, highlighting the strength of its standalone activity in this model. ATNM-400-containing regimens were favorably tolerated and prolonged survival relative to control groups. Following bevacizumab failure, ATNM-400 monotherapy retained activity, achieving 50% TGI with prolonged survival and favorable tolerability. These findings support development in treatment-resistant ovarian cancer. In the disseminated ID8-fLuc ovarian cancer model in immunocompetent mice, ATNM-400-containing regimens prolonged survival relative to their respective controls. Combinations with carboplatin and paclitaxel also prolonged survival compared with chemotherapy alone. Survival follow-up remained ongoing at the time of the presentation, with some animals in ATNM-400 treatment groups still alive. Preclinical Tolerability and Translational Development The studies generally showed favorable tolerability at the evaluated doses. In ovarian cancer studies, single-bolus and fractionated dosing produced minimal changes in assessed blood, liver and kidney markers. No treatment-related abnormalities were observed in the assessed markers in the HCT15 colorectal model; a slight ALT elevation was observed with ATNM-400 plus bevacizumab in the SW620 model. These findings support continued translational evaluation of ATNM-400 as monotherapy and in selected combinations. About ATNM‑400 and HER3 ATNM‑400 is an investigational antibody radioconjugate that pairs the HER3‑targeting monoclonal antibody barecetamab with the alpha‑emitting isotope Actinium‑225. Its antibody‑based design combines antigen‑specific targeting with the potential for sustained tumor localization, supporting prolonged delivery of high‑energy alpha radiation. Tumor uptake and retention observed through Day 7 with the ⁸⁹Zr‑labeled imaging counterpart support this development rationale alongside the approximately 10‑day half‑life of ²²⁵Ac. The theranostic approach enables noninvasive visualization of antibody distribution to inform therapeutic development. ATNM‑400 is differentiated from PSMA‑targeted radiotherapies by its focus on HER3, an antigen implicated in tumor survival and treatment resistance. PSMA‑directed approaches include Novartis' Pluvicto and a broad pipeline of investigational therapies, including Telix Pharmaceuticals' TLX591‑Tx, Clarity Pharmaceuticals' ⁶⁷Cu‑SAR‑bisPSMA, Convergent Therapeutics' CONV01‑α, AstraZeneca's AZD2265 (formerly FPI‑2265), Curium's lutetium‑177 zadavotide guraxetan (¹⁷⁷Lu‑PSMA‑I&T), ARTBIO's AB001 and AdvanCell's ADVC001. These programs span small‑molecule and antibody‑based therapies using beta‑ or alpha‑emitting isotopes. ATNM‑400 combines HER3 targeting with an Actinium‑225 antibody radioconjugate, offering a distinct biological approach with the potential to expand radiotherapy across the broad mCRPC population, including patients with PSMA‑low or PSMA‑negative disease and those who do not respond to or progress following PSMA‑directed treatment. Its HER3‑directed mechanism also supports investigation beyond prostate cancer in other HER3‑expressing solid tumors. HER3, also known as ERBB3, is a member of the epidermal growth factor receptor family involved in signaling pathways that support tumor growth, survival and resistance to treatment. HER3‑directed antibody‑drug conjugates in clinical development include BioNTech and MediLink's BNT326/YL202, Bristol Myers Squibb and SystImmune's EGFR × HER3 bispecific ADC izalontamab brengitecan (iza‑bren), and Daiichi Sankyo and Merck's patritumab deruxtecan (HER3‑DXd). These programs underscore the clinical development interest in HER3 as an oncology target. ATNM‑400 applies a distinct payload strategy, using alpha radiation in place of a conventional cytotoxic drug. Its preclinical activity in prostate, non‑small cell lung and breast cancer models supports investigation as a potential pan‑cancer radiotherapy, as a monotherapy and in rational combinations. About Actinium Pharmaceuticals, Inc. Actinium is a pioneer in targeted radiotherapies designed to improve outcomes for patients with cancer. The company employs a biology‑driven approach to develop differentiated radiopharmaceuticals for solid tumors and hematologic malignancies. Its mission is to transform cancer treatment through innovative radioconjugates that maximize therapeutic efficacy while minimizing toxicity to healthy tissue by combining expertise in tumor biology, translational medicine, and radiochemistry. Since inception, Actinium has focused on developing innovative radiotherapies. Its pipeline reflects this strategy across three areas: (1) solid tumor therapeutics including ATNM‑400 and Actimab‑A with pan‑tumor potential; (2) Actimab‑A as a therapeutic backbone for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in collaboration with the National Cancer Institute (NCI); and (3) targeted conditioning agents including Iomab‑B for bone marrow transplant and Iomab‑ACT for cell and gene therapy conditioning. ATNM‑400 targets HER3, an antigen distinct from PSMA, and is in a first‑in‑human Phase 1 study in mCRPC, with preclinical activity across metastatic castration‑resistant prostate cancer (mCRPC), non‑small cell lung cancer (NSCLC), and breast cancer. Actimab‑A has shown improved survival in relapsed/refractory AML with CLAG‑M and is advancing toward a Phase 2/3 trial, with additional development ongoing through a CRADA with the NCI. Actinium is also advancing preclinical solid tumor programs and holds ~250 patents and patent applications, including intellectual property related to cyclotron‑based production of Ac‑225. For more information, please visit 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. Investors: investorrelations@actiniumpharma.com View original content to download multimedia:https://www.prnewswire.com/news-releases/actinium-pharmaceuticals-presents-eanm-2026-results-reinforcing-atnm-400s-pan-tumor-potential-across-lung-colorectal-and-ovarian-cancer-models-302913279.html SOURCE Actinium Pharmaceuticals, Inc. Released October 20, 2026

Divarasib monotherapy demonstrated superior efficacy over first-generation KRAS G12C inhibitors, lowering the risk of disease progression or death by 42% and the overall risk of death by 44%, in the phase III Krascendo 1 study1,2 At the time of primary analysis, divarasib achieved a median overall survival of approximately 18 months, compared to 12 months for sotorasib or adagrasib1,2 No new safety signals were observed with divarasib; the most common treatment-related adverse events were mainly low grade and manageable1,2 Data presented as a late-breaking abstract during a Presidential Symposium at the 2026 ESMO Congress and simultaneously published in The New England Journal of Medicine1,2 25 October 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) announced today pivotal results from the phase III Krascendo 1 study, which demonstrated the superior efficacy of investigational divarasib, a next-generation KRAS G12C inhibitor, compared with current standard of care KRAS G12C inhibitors in people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).1,2 Participants treated with divarasib monotherapy lived significantly longer, lowering the risk of death by 44% compared with sotorasib or adagrasib (overall survival, OS, HR 0.56, [95% CI: 0.41-0.78], p=0.0005).1,2 Median OS for divarasib is currently approximately 18 months, compared to 12 months for the control arm (see table below).1,2 No new safety findings were observed with divarasib and the most common treatment-related adverse events (TRAEs) were mainly low grade and manageable.1,2 These data were presented as a late-breaking abstract during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine.1,2 “The phase III Krascendo 1 results demonstrate the potential for divarasib to become a new standard of care for people with previously treated KRAS G12C-mutated lung cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "The superior efficacy against the current standard of care demonstrated in this head-to-head trial reinforces divarasib's best-in-class profile. We are working closely with health authorities to bring this new treatment option to the people who need it.” The G12C mutation is one of the most common KRAS mutations, found in approximately one in eight people with NSCLC.3,4 Accumulating evidence suggests that people with NSCLC who have the KRAS G12C mutation may have poorer outcomes than those who have the unmutated KRAS gene (wild-type disease).5,6 Despite the approval of current, first-generation KRAS G12C-targeted treatments, there remains a significant unmet need for more effective therapy options. “New life-extending treatments are greatly needed, as most patients with this type of cancer will eventually relapse after initial therapy, and there are limited effective treatments for recurrent disease,” said study lead author Ferdinandos Skoulidis, MD, PhD, Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “The Krascendo 1 results highlight divarasib’s practice-changing potential, as the first KRAS inhibitor to meaningfully improve overall survival for people with previously treated KRAS G12C-mutated lung cancer, compared with current treatment options.” The Krascendo 1 study is the only global head-to-head study to evaluate a next-generation KRAS G12C inhibitor versus approved first-generation KRAS G12C inhibitors.1,2 The study met primary and key secondary endpoints, and divarasib demonstrated statistically significant and clinically meaningful improvements in OS and progression-free survival (PFS) over sotorasib or adagrasib.1,2 Key efficacy results from the phase III Krascendo 1 study:1,2 *Assessed in response-evaluable population (n=328; ten patients [divarasib arm, n=6; control arm, n=4] did not have measurable disease at baseline and were excluded from the response-evaluable set). Duration of Response (DOR) evaluated in those who responded to treatment (divarasib arm, n=94; control arm, n=54). The safety pro divarasib monotherapy was consistent with the known class effects of KRAS G12C inhibitors.1,2 The most common TRAEs comprised GI toxicity (most commonly, diarrhoea, nausea, and vomiting) and hepatotoxicity.1,2 Fewer participants discontinued treatment due to TRAEs with divarasib (4.8% versus 11.7%) and the rate of serious TRAEs was approximately half that of sotorasib or adagrasib (7.8% versus 15.2% respectively), despite patients remaining on treatment for more than twice as long (11.3 months compared with 5.0 months).1,2 Roche is advancing a comprehensive phase III clinical development programme in NSCLC, investigating divarasib as both a monotherapy and as a chemotherapy-free combination, across different disease settings and lines of therapy. The US Food and Drug Administration granted Breakthrough Therapy Designation to divarasib in 2022, and in 2026, Orphan Drug Designation for KRAS G12C-mutated NSCLC. The Krascendo 1 study [NCT06497556] is the only global head-to-head study evaluating a Kirsten rat sarcoma virus (KRAS) G12C inhibitor in direct comparison with first-generation approved KRAS G12C inhibitors. This phase III, randomised, open-label, multicentre study evaluates the efficacy and safety of divarasib monotherapy versus sotorasib or adagrasib in people with previously treated KRAS G12C-mutated advanced or metastatic non-small cell lung cancer. The study includes 338 adults, randomised to receive either divarasib once daily (n=167) or, either sotorasib once daily or adagrasib twice daily (n=171). The primary endpoint is blinded independent central review (BICR)-assessed progression-free survival. Secondary endpoint measures include overall survival, confirmed objective response, duration of response, as well as other efficacy and safety measures. Divarasib is an investigational, best-in-class, next-generation, oral, KRAS G12C inhibitor, discovered and developed by researchers within Roche and Genentech. It has shown greater potency and selectivity in preclinical studies compared with first-generation KRAS G12C-targeting treatments, sotorasib or adagrasib, with superior efficacy demonstrated in people with previously treated KRAS G12C-mutated NSCLC.1,2,7 Divarasib is designed to selectively bind to the KRAS G12C protein, locking the protein in an inactive (off) state, thereby turning off its tumour-driving signalling.7,8,9 Divarasib’s comprehensive clinical development programme is anchored by three phase III studies: Divarasib underpins Roche’s diversified pipeline targeting the RAS signalling pathway, including other mutant-selective inhibitors and a pan-RAS inhibitor, designed to extend the benefits of RAS inhibition strategies to more patients. Despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths worldwide, surpassing the combined mortality rates of breast, prostate, and stomach cancers.10,11 Each year, it claims the lives of 1.8 million people, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases.10,12 KRAS is one of the most frequently mutated genes in lung cancer, occurring in approximately 25% of newly diagnosed lung cancers, and is associated with poor prognosis for patients.9 The G12C mutation is one of the most common KRAS mutations, found in approximately 12-14% of NSCLC cases.3,4 The KRAS gene produces the KRAS protein, which acts as a cellular control switch, cycling between an active (on) and inactive (off) state to regulate cell growth and proliferation, making it a critical target for new therapeutic strategies.9 G12C mutation locks the KRAS protein in its active (on) state, leading to continuous, unregulated signalling for cell growth, driving tumour proliferation.8,9 Roche is committed to advancing the field of lung cancer treatments, leveraging more than 20 years of deep scientific expertise to improve patient outcomes and their overall experience. Roche’s strong commitment to investment in research and development has built a robust portfolio of approved medicines and companion diagnostics, which empowers physicians to better understand a patient's disease and optimise care. Roche’s broad portfolio includes approved medicines such as Alecensa® (alectinib), Tecentriq® (atezolizumab), and Rozlytrek® (entrectinib). Its extensive pipeline includes investigational treatments across three key focus areas: small cell lung cancer, non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), and NSCLC without AGA. Utilising diverse approaches, ranging from cancer-cell-killing ‘cytotoxics’ and immunotherapies to treatments targeting specific characteristics of cancer cells, we aim to translate scientific discoveries into meaningful progress in patient care. Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions. Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them. Genentech in the United States is a fully owned subsidiary in the Roche Group. 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