On October 21, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the final data from the global Phase III ALEX study (NCT02075840) and the latest results from the global Phase III ALINA study (NCT03456076) of its anti-cancer agent/ALK inhibitor Alecensa (generic name: alectinib) for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Annual Congress.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the final analysis of overall survival (OS), a secondary endpoint of the ALEX study, the median survival time for Alecensa was 81.1 months compared to 54.2 months for crizotinib (hazard ratio[HR]=0.78, 95% CI: 0.56-1.08).1
This survival advantage was consistent across all subgroups, including those with central nervous system metastases. The median duration of response was approximately four times longer with Alecensa compared to crizotinib (42.3 months vs 11.1 months, HR=0.41, 95% CI: 0.30-0.56), and the safety profile was consistent with the known profile of Alecensa. The main adverse event (≥30%) was constipation (40.1%), and despite a longer median treatment duration with Alecensa compared to crizotinib (28.1 months vs. 10.8 months), no new or unexpected safety signals were observed.1

Updated results from the ALINA study (NCT03456076) were also presented at ESMO (Free ESMO Whitepaper) 2025. ALINA is the Phase III trial of an ALK inhibitor with demonstrated efficacy in resectable stage IB-IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC. In the primary analysis, Alecensa showed a significant disease-free survival (DFS) benefit compared to chemotherapy (HR=0.24, 95% CI: 0.13-0.43, p<0.001).2

After a median follow-up of four years, Alecensa continued to show improved DFS compared to chemotherapy in stage II-IIIA and stage IB-IIIA (ITT: intent-to-treat) patient populations. Alecensa reduced the risk of recurrence or death by 64% compared to platinum-based chemotherapy in completely resected stage II-IIIA ALK-positive NSCLC (HR=0.36, 95% CI: 0.23-0.56) and by 65% in the ITT population with completely resected stage IB-IIIA ALK-positive NSCLC (HR=0.35, 95% CI: 0.23-0.54). This DFS improvement was consistently demonstrated across subgroups, and a clinically meaningful improvement in CNS DFS was also maintained. Regarding safety, results were consistent with the primary analysis, with no new safety concerns or unexpected issues identified.2

About ALEX study

The ALEX study (NCT02075840/B028984) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of Alecensa (alectinib) versus crizotinib in treatment-naïve ALK-positive NSCLC. Patients were randomly assigned in a 1:1 ratio to receive either Alecensa or crizotinib. Crossover between treatment groups before disease progression was not permitted. In the ALEX study, alectinib was administered orally at 600 mg twice daily, which differs from the approved dosage and administration in Japan.
The primary endpoint of the ALEX study is progression-free survival (PFS) as assessed by the investigator. Secondary endpoints include PFS as assessed by an Independent Review Committee, time to central nervous system progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life, and safety. This multicenter study was conducted in 303 patients across 161 sites in 31 countries.

About ALINA study
The ALINA study (NCT03456076) is a randomized, active-controlled, multicenter, open-label Phase III study evaluating the efficacy and safety of adjuvant Alecensa compared with platinum-based chemotherapy in resected Stage IB (tumor ≥4 cm) to IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC. The study enrolled 257 patients who were randomly assigned to either the Alecensa or chemotherapy treatment arm. The primary endpoint is disease-free survival. Secondary endpoints include overall survival and the percentage of patients experiencing adverse events.

About Alecensa
Alecensa is a highly selective, central nervous system-active, oral medicine created at Chugai Pharmaceutical Co., Ltd. for people with non-small cell lung cancer (NSCLC) whose tumors are identified as anaplastic lymphoma kinase (ALK) positive. ALK fusion / rearrangement gene-positive lung cancer is found in approximately 3-5% of NSCLC cases.5 Alecensa is already approved in over 100 countries as an initial (first-line) and second-line treatment for ALK fusion / rearrangement gene-positive metastatic NSCLC, including in the United States, Europe, Japan, China, and Taiwan. For adjuvant therapy of ALK fusion / rearrangement gene-positive NSCLC, Alecensa received approval in the United States in April 2024, followed by Europe in June 2024, and Japan in August 2024. In Japan, Alecensa has been approved for "ALK fusion gene-positive unresectable, advanced or recurrent non-small cell lung cancer," "adjuvant therapy of ALK fusion-positive non-small cell lung cancer," and "recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma."

Trademarks used or mentioned in this release are protected by law.

(Press release, Chugai, OCT 21, 2025, View Source [SID1234656862])

On October 21, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported that the United States Patent and Trademark Office (USPTO) has granted US Patent No. 12,448,465, covering the composition of matter of ATOR-4066, the company’s bispecific antibody targeting CD40 and CEACAM5. The patent will formally issue on 21 October 2025.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The granted patent provides broad protection for ATOR-4066, including the bispecific antibody itself and its unique binding regions targeting CD40 and CEACAM5, and is expected to remain in force until 2043, excluding any potential patent term extensions.

ATOR-4066 is a novel bispecific antibody designed to activate CD40 on antigen-presenting cells while simultaneously targeting CEACAM5 on tumor cells. By bridging immune activation and tumor recognition, ATOR-4066 has demonstrated potent preclinical anti-tumor activity. The candidate is advancing toward clinical development as part of Alligator’s next-generation immuno-oncology pipeline. The program builds on Alligator’s extensive experience with mitazalimab, its lead CD40 agonist currently advancing toward pivotal development in pancreatic cancer.

"This patent grant marks an important milestone in strengthening the intellectual property protection around ATOR-4066," said Søren Bregenholt, CEO of Alligator Bioscience. "It underscores the innovation behind our bispecific antibody platform and reinforces the long-term value of our pipeline as we continue to advance novel immunotherapies toward the clinic."
Alligator has an additional continuation application pending in this patent family in the United States, further expanding the scope of protection around ATOR-4066.

(Press release, Alligator Bioscience, OCT 21, 2025, https://mfn.se/a/alligator-bioscience/alligator-bioscience-granted-us-patent-covering-ator-4066-bispecific-antibody [SID1234656861])

On October 21, 2025 SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany, reported that long-term efficacy and safety data from the Phase 3 DeFi trial of OGSIVEO (nirogacestat), an oral gamma secretase inhibitor for the treatment of adults with progressing desmoid tumors who require systemic treatment, were published in the Journal of Clinical Oncology (JCO). The long-term follow-up data from DeFi, which was a global, randomized, multicenter, double-blind, placebo-controlled trial, were previously presented at the 2024 Connective Tissue Oncology Society Meeting. The new results published in JCO utilized a December 2024 data cutoff date (the final data cut of the clinical trial) and showed that longer-term treatment with OGSIVEO was associated with further reductions in tumor size, an increase in objective response rate (ORR) with additional partial responses (PRs) and complete responses (CRs), sustained improvement in patient reported outcomes, and a consistent safety profile compared to the April 2022 data cut off utilized for the primary analysis of the trial. The JCO e-publication can be accessed at the following link: View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Desmoid tumors are locally aggressive and complex tumors whose unpredictable growth can cause significant pain, functional impairment, and emotional distress. For many patients, these tumors disrupt daily life in ways that are often underestimated, so advancing treatment options that offer durable symptom relief and tumor control can make a meaningful difference for patients," said Ravin Ratan, M.D., M.Ed., Associate Professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston and lead author of the JCO publication. "While the optimal duration of therapy may vary for many patients and is best decided between individual patients and their physicians, the new data published in the JCO provide physicians with additional information regarding the long-term safety and efficacy of nirogacestat, and will help inform treatment decisions and improve patient care."

In the Phase 3 DeFi trial primary analysis, which was previously published in the New England Journal of Medicine, OGSIVEO showed significant improvement versus placebo in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PRO) in adult patients with progressing desmoid tumors (DT; median [range] exposure: 20.6 [0.3-33.6] months).1 In the JCO publication, long-term efficacy and safety were evaluated in patients randomized to OGSIVEO and followed through the final data-cutoff date of December 2024. The median duration of OGSIVEO treatment in these patients was 33.6 (0.3 to 61.8) months.

Objective response rates (ORR) improved with long-term OGSIVEO treatment. While ORR was 34.3% (n = 24) in year 1, it increased to 45.7% (n = 32) in patients who received OGSIVEO for up to 4 years, with three additional complete responses (CRs) and three additional partial responses (PRs) since the primary analysis and yielding 24 (34.3%) PRs and 8 (11.4%) CRs in total. The median best percent reduction from baseline in target tumor size by RECIST 1.1 with continuous OGSIVEO treatment was −32.3% at year one (n=46) and −75.8% (n=15) for patients completing at least four years of treatment. Improvements in patient-reported outcomes (PROs) of pain, desmoid tumor-specific symptom severity, desmoid tumor-specific physical functioning, global health status/quality of life and role functioning occurred early (as early as Cycle 2, the first post-treatment timepoint evaluated as disclosed at the primary analysis) and were sustained with up to 45 months of treatment with OGSIVEO.

Overall, the incidence and severity of frequently reported treatment emergent adverse events (TEAEs) decreased through years two, three and four of treatment. The most common adverse events (>15%) reported in patients receiving OGSIVEO were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Please see Important Safety Information below, including Warnings & Precautions relating to diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity.2

"We are pleased that long-term continuous nirogacestat treatment for up to four years was associated with additional late responses and further tumor size reductions," said Uche Iloeje, M.D., Senior Vice President, Global Head of Medical Affairs at SpringWorks Therapeutics. "These data represent the largest prospective analysis from a randomized controlled clinical trial of long-term exposure to any systemic agent for desmoid tumors and provide valuable insights on the benefits of OGSIVEO for patients with desmoid tumors."

About the DeFi Trial

DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate, duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes. DeFi also included an open-label extension phase.

About Desmoid Tumors

Desmoid tumors are rare, locally aggressive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.3,4

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.5,6 In the U.S., up to 1650 people are diagnosed with desmoid tumors every year.5,7,8

Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.6,9 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.10,11

About OGSIVEO (nirogacestat)

OGSIVEO (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States and European Union as monotherapy for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

The FDA and the EMA have granted Orphan Drug designation for OGSIVEO for the treatment of desmoid tumors.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Diarrhea: Diarrhea occurred in 84% of patients treated with OGSIVEO. Grade 3 events occurred in 16% of patients. Monitor patients and manage using antidiarrheal medications. Modify dose as recommended.
Ovarian Toxicity: Female reproductive function and fertility may be impaired in patients treated with OGSIVEO. Impact on fertility may depend on factors like duration of therapy and state of gonadal function at time of treatment. Long-term effects on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness.
Hepatotoxicity: ALT or AST elevations occurred in 30% and 33% of patients, respectively. Grade 3 ALT or AST elevations (>5 × ULN) occurred in 6% and 2.9% of patients. Monitor liver function tests regularly and modify dose as recommended.
Non-Melanoma Skin Cancers: New cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment.
Electrolyte Abnormalities: Decreased phosphate (65%) and potassium (22%) occurred in OGSIVEO-treated patients. Phosphate <2 mg/dL occurred in 20% of patients. Grade 3 decreased potassium occurred in 1.4% of patients. Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended.
Embryo-Fetal Toxicity: Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at maternal exposures below human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose.
ADVERSE REACTIONS

The most common (≥15%) adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
Serious adverse reactions occurring in ≥2% of patients were ovarian toxicity (4%).
The most common laboratory abnormalities (≥15%) were decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
DRUG INTERACTIONS

CYP3A Inhibitors and Inducers: Avoid concomitant use with strong or moderate CYP3A inhibitors (including grapefruit products, Seville oranges, and starfruit) and strong or moderate CYP3A inducers.
Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors and H2 blockers. If concomitant use cannot be avoided, OGSIVEO can be staggered with antacids (e.g., administer OGSIVEO 2 hours before or 2 hours after antacid use).
Consult the full Prescribing Information prior to and during treatment for important drug interactions.
To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for OGSIVEO for more information.

(Press release, SpringWorks Therapeutics, OCT 21, 2025, View Source [SID1234656824])

On October 20, 2025 Upthera (CEO Si-Woo Choi), a company specializing in the development of innovative new drugs based on Targeted Protein Degradation (TPD) technology, reported that it has received approval from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for a Phase 1/2a clinical trial of its PLK1-targeted protein degradation-based (TPD) drug candidate ‘UP1002’ for small cell lung cancer (SCLC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This approval marks the first global entry into clinical trials for a new TPD-class drug targeting PLK1, and is considered an achievement that demonstrates Upthera’s proprietary protein degradation technology and global competitiveness. Next year, we plan to proceed with the IND approval process in Korea as well to expand the global clinical trials of ‘UP1002’ in earnest.

The clinical trial approved this time is a Phase 1/2a combined design that proceeds to confirm safety and tolerability through initial dose escalation, followed by evaluating efficacy indicators through an expansion cohort. Uptera aims to administer the drug to the first patient starting next year, involving 30 to 60 patients in the U.S., and plans to consider expanding to other solid tumor indications depending on future results.

Small cell lung cancer (SCLC) has been known for decades as a cancer where new drug development is significantly more difficult compared to other types of cancer, and even recently approved drugs have limited anticancer efficacy, such as extending survival.

In addition, it is an intractable cancer with a very low 5-year survival rate of less than 7% due to the rapid rate of tumor metastasis and high recurrence rate. While the development of numerous targeted anticancer drugs based on reliable biomarkers is underway for non-small cell lung cancer, the development of targeted anticancer drugs for small cell lung cancer is difficult due to the lack of accurate biomarkers.

To overcome these limitations, Upthera is developing ‘UP1002,’ a novel drug candidate that directly degrades PLK1 (Polo-like kinase 1), a key protein regulating cell division, by utilizing TPD technology. PLK1 is an essential protein (kinase) that regulates cell division during the cell cycle (G2/M phase) and is overexpressed in rapidly proliferating cells, such as cancer cells. While numerous global pharmaceutical companies, including Boehringer Ingelheim and Takeda, have developed PLK1 inhibitors (small molecule inhibitors), most have been discontinued during clinical trials due to dose-limiting toxicity (DLT). To date, there are no approved drugs with a mechanism that selectively inhibits or degrades PLK1.

UP1002 is characterized by inducing an anticancer effect even at lower concentrations than existing inhibitors by directly degrading the PLK1 protein, and by fundamentally overcoming the problem of dose-limiting toxicity (DLT). This mechanism is a novel approach that induces apoptosis by halting the cell cycle of cancer cells, and is expected to lead a paradigm shift in treatment for cancers with rapid cell proliferation, such as small cell lung cancer.

Upthera’s UP1002 (PLK1) was recognized for its innovation and technological capabilities and was selected as a project under the Korea Drug Development Fund (KDDF) ​​in 2022, receiving support. Based on the Global RA support program within the KDDF, Upthera has established a global clinical development strategy in collaboration with global clinical research institutions such as QubeST Bio and KCRN Research.

UP1002 is recognized as the first-in-class anticancer drug that degrades PLK1 and the first clinical pipeline in the TPD industry to target cell cycle-related proteins, which are difficult to develop. In addition, Upthera has filed 82 domestic and international patents related to UP1002, 19 of which have been registered. The company plans to continuously strengthen its patent portfolio and build patent barriers to effectively block the entry of latecomers in the PLK1 degradation field and solidify its position as a first mover.

"This FDA IND approval is an achievement that officially recognizes Upthera’s proprietary protein degradation technology and global development capabilities," said Choi Si-woo, CEO of Upthera. "We will present new treatment options to patients with small cell lung cancer through clinical results and strengthen our global competitiveness in the TPD field."

(Press release, Uppthera, OCT 20, 2025, View Source [SID1234664781])

On October 20, 2025 CIS BIOPHARMA AG, a company pioneering new cancer targets, reported that the company will present an abstract & poster about its lead ADC called CBO-001 at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) -AACR- NCI-EORTC- AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, CIS BIOPHARMA, OCT 20, 2025, View Source [SID1234657093]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The AACR (Free AACR Whitepaper)-NCI-EORTC will be held October 22-26, 2025, at the Boston Hynes Convention Center in Boston, Massachusetts. The poster highlights preclinical data on CBO-001, a proprietary antibody-drug conjugate (ADC) developed by CIS BIOPHARMA. "We are excited to share our preclinical data at this year’s AACR (Free AACR Whitepaper)-NCI-EORTC meeting, demonstrating exceptional efficacy of our L1CAM ADC in several cancer indications, with outstanding results in small-cell lung cancer and ovarian cancer," says Dominik Brücher, Ph.D., Chief Technology Officer of CIS BIOPHARMA AG.

"The superior pre-clinical efficacy of this emerging cancer target versus standard-of-care and other emerging targets such as B7H3 and DLL3 in SCLC, positions us in a unique competitive situation, also envisioning combination strategies with these. Our overall goal with CBO-001 is to develop therapeutic options with superior overall survival for patients with SCLC, OC and other L1CAM positive malignancies."