On October 18, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III evERA Breast Cancer study. Data showed giredestrant in combination with everolimus significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 44% and 62% in the intention-to-treat (ITT) and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. The evERA study is evaluating the investigational giredestrant combination in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This is the first positive head-to-head Phase III trial investigating a selective estrogen receptor degrader-containing regimen versus a standard-of-care combination. The results are being presented in an oral session at the European Society for Medical Oncology Congress 2025. Data will be shared with health authorities, with the aim of bringing this potential treatment option to people as soon as possible.

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"A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors. These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development.

"Resistance to standard-of-care therapies is common in the post-CDK inhibitor setting, and the results from evERA validate using a combination to address this challenge," said Erica L. Mayer, M.D., Medical Oncologist at Dana-Farber Cancer Institute. "The clinically meaningful benefit observed with the giredestrant and everolimus all-oral combination is impressive and speaks to its potential to improve outcomes for patients in need of new treatment options."

The giredestrant combination demonstrated a statistically significant and clinically meaningful improvement in PFS compared with standard-of-care endocrine therapy plus everolimus. In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arm, respectively (stratified hazard ratio [HR]=0.56; 95% CI: 0.44-0.71, p-value= <0.0001). In the ESR1-mutated population, the median PFS was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively (HR=0.38; 95% CI: 0.27-0.54, p-value= <0.0001). The PFS benefit was consistent across pre-specified subgroups in both populations. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566). Follow-up for OS will continue to next analysis. Giredestrant in combination with everolimus also demonstrated improvements in key secondary endpoints (objective response rate and duration of response) compared with the comparator arm across both patient populations.

Adverse events for the giredestrant-based combination were manageable and consistent with the known safety profiles of the individual medicines. No new safety signals were observed, including no photopsia.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes. All-oral combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signaling pathways while helping to minimize the impact of treatment on people’s lives without the need for injections.

Our extensive giredestrant clinical development program spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

About the evERA Breast Cancer study

evERA Breast Cancer [NCT05306340] is a Phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomization to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.

About estrogen receptor (ER)-positive breast cancer

Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining feature of ER-positive breast cancer is that its tumor cells have receptors that attach to estrogen, which can contribute to tumor growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

About giredestrant

Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist.

Giredestrant is designed to block estrogen from binding to the estrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.

Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

(Press release, Genentech, OCT 18, 2025, View Source [SID1234656757])

On October 18, 2025 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported data from the dose escalation portion of the Phase 1/2 study of JK06, a 5T4-targeted antibody drug conjugate (ADC), in patients with unresectable locally advanced or metastatic cancer, including non-small cell lung cancer (NSCLC) and breast cancer, which is being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

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Data presented at ESMO (Free ESMO Whitepaper) include 34 patients enrolled in Europe with advanced relapsed/refractory solid tumors who were treated with JK06, once every three weeks, across five dose levels (1.5-8.0 mg/kg) in dose escalation. Among the 34 patients, 29 were response-evaluable, all having failed standard of care therapy, and among whom 83% had received three or more prior lines of treatment and 59% had received four or more prior lines of therapy at the time of enrollment.

Key efficacy findings among the 29 response-evaluable patients include:

6 patients attained confirmed partial responses (PRs) (21%).
Among 13 NSCLC patients, 5 attained confirmed PRs (ORR 38%), with the longest duration of response lasting 30 weeks.
Among 7 response-evaluable breast cancer patients, 1 attained a confirmed PR with a duration of response lasting 18 weeks.
PRs were observed at 3.0 mg/kg (1 NSCLC), 4.5 mg/kg (3 NSCLC and 1 breast cancer), and 6.0 mg/kg (1 NSCLC).
Treatment with JK06 has been generally well-tolerated with predominantly low grade (Grades 1 and 2), manageable toxicities, such as fatigue, alopecia, decreased appetite, dry eye and diarrhea. Among treatment-related adverse events (TRAEs) occurring in at least 5% of patients, only the following ≥ Grade 3 events were observed:

At dose levels 1.5-3.0 mg/kg (n=12 patients), 1 patient with Grade 3 peripheral neuropathy.
At dose level 4.5 mg/kg (n=15 patients), 1 patient with Grade 3 keratitis.
At dose levels 6.0-8.0 mg/kg (n=7 patients), 1 patient with Grade 3 fatigue, 1 patient with Grade 3 ALT increase, and 1 patient with Grade 5 pneumonitis.
Pharmacokinetic analysis demonstrated free monomethyl auristatin E (MMAE) levels that were favorable at dose levels up to 4.5 mg/kg.
"We are encouraged by the promising preliminary data demonstrating the combination of safety and efficacy of JK06 among heavily pre-treated metastatic solid tumors, including in NSCLC and breast cancer, supporting our belief that JK06 has the potential to be a first-in-class, differentiated therapy for patients with 5T4-expressing cancers," said Sam Murphy, Chief Executive Officer of Salubris Biotherapeutics. "We look forward to advancing the study into dose expansion in tumor-specific cohorts for NSCLC and breast cancer, while continuing to explore activity in other solid tumors known to overexpress 5T4, as we aim to improve outcomes for these patients with advanced, aggressive disease and limited therapeutic options."

The Phase 1/2 open-label, dose-escalation and expansion study (NCT06667960) to assess the safety, pharmacokinetics, and preliminary efficacy of JK06 is ongoing, and the cohort expansion phase, which is currently enrolling, will determine the recommended Phase 2 dose for further development.

Details of the ESMO (Free ESMO Whitepaper) presentation are as follows:

Title: A Phase 1/2 Study of JK06, a 5T4-Targeted Antibody Drug Conjugate (ADC), in Patients with Unresectable Locally Advanced or Metastatic Cancer
Presenter: Nuria Kotecki, M.D. at Institut Jules Bordet, Anderlecht, Belgium
Abstract #: 961P
Session: Developmental Therapeutics
Date/Time: Sunday, October 19, 2025 | 12:00 – 1:00 PM CEST

About JK06

JK06 is a first-in-class quadrivalent, biparatopic ADC that selectively targets 5T4 with a monomethyl auristatin E (MMAE) payload. 5T4 is an oncofetal protein that is overexpressed in a wide range of solid tumors, including NSCLC, breast, renal and genitourinary cancers, and is associated with more aggressive tumor progression and reduced survival. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies.

(Press release, Salubris Biotherapeutics, OCT 18, 2025, View Source [SID1234656756])

On October 18, 2025 SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing next-generation immunotherapies for infectious diseases and their associated cancers, reported the presentation of first-in-human clinical data for SCG142 in an investigator-initiated Phase I trial (NCT06544720) in patients with recurrent or metastatic HPV-associated carcinomas. The poster will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany, on Saturday, 18 October 2025.

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This ongoing first-in-human trial evaluates the safety, tolerability and preliminary efficacy of SCG142, a novel human papillomavirus (HPV) E7-specific T-cell receptor-engineered T (TCR T) cell therapy armoured with a TGFβRII-41BB chimeric switch receptor. Eligible patients are HLA-A*02:01-positive with advanced HPV16- or HPV52-positive carcinomas who have progressed on or were intolerant to at least one prior systemic therapy. Key endpoints include safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. As of the data cut-off, tumor shrinkage was observed in all seven treated patients, resulting in a disease control rate (DCR) of 100%. Four of the seven patients (57%) achieved >30% tumor reduction, including two confirmed partial responses (PR) and two unconfirmed PRs. No dose-limiting toxicities or serious adverse events were reported. These preliminary findings support continued clinical development of SCG142.

"SCG142 is a novel and differentiated HPV-specific TCR T cell therapy with promising clinical activity." said Prof. Dr. Yang Li, Director of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University. "We’re excited that tumor shrinkage was observed in all seven treated patients and that SCG142 was well tolerated. These encouraging preliminary findings underscore the potential of SCG142 to provide new solutions for patients in a variety of HPV16 and HPV52 expressing cancers and support further evaluation in larger patient cohorts", she added.

SCG142 was isolated with GianTCRTM, SCG’s proprietary TCR screening platform with the ability to identify fully natural TCRs with high affinity and high avidity properties as well as potent antiviral and anti-tumor effects against infection-related solid tumors accompanied by a lower risk of off-target toxicity. "We are delighted that the excellent preclinical profile of our HPV-E7-specific TCR – including high avidity and dual functionality in both CD8+ and CD4+ T cells – has translated into clinical activity with SCG142" added Dr. Susanne Wilde, VP, Head of Preclinical Research of SCG Cell Therapy.

Besides SCG142, SCG is also advancing SCG101, a hepatitis B virus (HBV)-specific TCR T cell therapy for the treatment of HBV-related hepatocellular carcinoma (HCC).

(Press release, SCG Cell Therapy, OCT 18, 2025, View Source [SID1234656750])

On October 18, 2025 Florida Cancer Specialists & Research Institute, LLC (FCS) reported it will be in the spotlight this week in Berlin at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. Among the 23 studies co-authored by FCS physician investigators selected for presentation to oncology experts worldwide, one has earned the distinction of being featured as an oral presentation and four as poster presentations by FCS first authors.

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23 Florida Cancer Specialists & Research Institute abstracts are being presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany including one oral presentation by FCS Director of Drug Development Manish R. Patel, MD, and four additional poster presentations by FCS first-authors.
23 Florida Cancer Specialists & Research Institute abstracts are being presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany including one oral presentation by FCS Director of Drug Development Manish R. Patel, MD, and four additional poster presentations by FCS first-authors.
"FCS is engaged in significant and transformative scientific discoveries that are driving new possibilities and better outcomes for patients everywhere," said Lucio N. Gordan, MD, FCS president & managing physician.

The following physician leader is first author of an oral presentation at the ESMO (Free ESMO Whitepaper) Congress:

Manish R. Patel, MD, FCS director of drug development, will participate in an oral presentation followed by expert discussion and perspectives of initial results of a first-in human study: A tumor-associated Mucin 1 (TA-MUC1)–directed Antibody–drug Conjugate (ADC), in Patients (pts) with Advanced/Metastatic (adv/met) Solid Tumors.
The following physician leaders are first authors of poster presentations at the ESMO (Free ESMO Whitepaper) Congress:

Bradley Monk, MD, FCS medical director of late-phase clinical research, will present the following abstracts:
Post hoc survival outcomes based on initial and subsequent treatment in patients (pts) with mismatch repair proficient/microsatellite stable (MMRp/MSS) primary advanced or recurrent endometrial cancer (pA/R EC) in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial.
Tisotumab Vedotin Plus Carboplatin or Pembrolizumab in Recurrent or Metastatic Cervical Cancer: 5-Year Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study.
Cesar Augusto Perez, MD, FCS, director of drug development, Sarah Cannon Research Institute (SCRI) at FCS, will review and discuss in a poster presentation, Phase 1/2 study of the next-generation Nectin-4-targeting antibody–drug conjugate CRB-701 (SYS6002) in patients with urothelial and non-urothelial solid tumours.
Judy S. Wang, MD, FCS associate director of drug development will present and discuss the findings of the following abstract: Histological biomarker analysis of nonclinical and baseline tumor samples from the phase 1 dose escalation study assessing micvotabart peliodotin (MICVO) in advanced solid tumors.
Dr. Patel, who oversees early phase research at FCS’ three drug development units, said, "Our team is proud to be at the forefront of oncology research, leading first-in-human studies and advancing cutting-edge targeted therapies."

Dr. Monk leads initiatives to expand and deploy late-phase clinical trials. He noted, "By pushing the boundaries of what’s possible, we’re helping bring the next generation of treatments to patients who need them most and are dedicated to increasing clinical trial accessibility to patients worldwide."

FCS researchers have also co-authored numerous abstracts that will also be featured in poster presentations throughout the annual international symposium:

Barry Berman, MD, MS: Clinical and biomarker results from E7386 study 102: Global dose-expansion cohort of E7386 + envatinib in patients with advanced/recurrent endometrial cancer that progressed on platinum-based chemotherapy and an anti−PD-(L)1 immunotherapy
Bradley Monk, MD:
Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. (Simultaneous publication in the Annals of Oncology.)
Human papillomavirus integration site mapping in advanced cervical cancer: The NRG Oncology/GOG-0240 NIH Cancer Moonshot.
Second progression-free survival (PFS2) and subsequent treatment in patients (pts) with folate receptor alpha (FR⍺)-positive platinum-resistant ovarian cancer (PROC) treated with mirvetuximab soravtansine (MIRV) vs investigator’s choice chemotherapy (ICC): Phase III MIRASOL trial.
5-year progression-free survival (PFS) with rucaparib (RUCA) maintenance in patients with newly diagnosed advanced ovarian cancer in ATHENA-MONO (GOG-3020/ENGOT-ov45). (Simultaneous publication in the Annals of Oncology.)
The relationship between patient-reported outcomes and clinician-rated toxicity in participants with locally advanced cervix cancer in the OUTBACK trial.
GOG-3119/ENGOT-en29/TroFuse-033: A Phase 3, Randomized Study of Sacituzumab Tirumotecan Plus Pembrolizumab vs Pembrolizumab Alone as First-Line Maintenance Therapy for Mismatch Repair-Proficient Endometrial Cancer.
BELLA: A Phase 2 Study of Relacorilant Plus Nab-Paclitaxel +/- Bevacizumab in Patients with Gynecologic Cancers.
Manish R. Patel, MD:
A phase 1 study of the next-generation farnesyltransferase inhibitor (FTI) KO-2806 as monotherapy in advanced solid tumors.
COM701 in ovarian cancer: A pooled analysis of 3 phase I clinical trials.
Farnesyltransferase inhibitor (FTI) KO-2806 in combination with cabozantinib (cabo) in renal cell carcinoma (RCC): Preliminary results from FIT-001 Phase 1 trial.
Single-agent divarasib experience in patients with KRAS G12C-positive pancreatic adenocarcinoma (panc), cholangiocarcinoma (cholangio), and other solid tumors.
Cesar Augusto Perez, MD:
Tipifarnib (TIP) and alpelisib (ALP) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 1 results from KURRENT-HN.
Phase 1 global study of Iza-Bren (BL-B01D1), an EGFR × HER3 bispecific antibody–drug conjugate (ADC), in patients with metastatic or unresectable NSCLC and other solid tumours.
Judy S. Wang, MD:
First- in- Human Study of the First-in-class Non-cellular Targeting Antibody-Drug Conjugate (ADC), MICVO, in Patients with Select Solid Tumors.
Phase 1 Expansion Study of the First-in-class Non-cellular Targeting Antibody-Drug Conjugate (ADC), Micvotabart Pelidotin (MICVO), in Patients with Select Advanced Solid Tumors.
FCS provides access to advanced clinical trial options across 29 locations in Florida, bringing promising therapies closer to home for cancer patients. Over 110 new early-phase and 40 late-phase studies are launched annually. FCS has played a vital role in the development of numerous cancer drugs approved by the U.S. Food and Drug Administration (FDA).

A longstanding partnership with Sarah Cannon Research Institute (SCRI), one of the world’s leading oncology research organizations conducting community-based clinical trials, provides patients with access to a comprehensive listing of clinical trials available in the U.S. Additionally, a partnership with Paradigm Health, Inc. helps streamline and accelerate matching patients to available clinical trials.

Representing more than 45,000 members globally, ESMO (Free ESMO Whitepaper) is a reference for oncology education and information. The ESMO (Free ESMO Whitepaper) Congress is a globally influential oncology platform for clinicians, researchers, patient advocates, journalists and healthcare industry representatives from all over the world. All of the accepted abstracts will be published online at ESMO (Free ESMO Whitepaper).

(Press release, Florida Cancer Specialists & Research Institute, OCT 18, 2025, View Source;research-institute-shaping-the-future-of-cancer-care-at-global-congress-302587904.html [SID1234656749])

On October 18, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported preliminary data from the ongoing ALKOVE-1 Phase 1/2 clinical trial of neladalkib, an investigational ALK-selective inhibitor, in patients with advanced ALK-positive solid tumors outside of non-small cell lung cancer (NSCLC). These data will be presented during a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025, taking place October 17-21, 2025, in Berlin, Germany, and are available on Nuvalent’s website at www.nuvalent.com.

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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

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"Neladalkib was designed with the goal of being a best-in-class ALK-selective inhibitor, and initial clinical safety and efficacy data have been reported in TKI pre-treated ALK-positive NSCLC with topline pivotal data expected by the end of this year. Today, we’re excited to share the first report of neladalkib’s encouraging preliminary activity beyond NSCLC, which continue to demonstrate its target characteristics of activity against ALK and ALK resistance mutations, brain penetrance, and avoidance of TRK inhibition associated with off-target CNS adverse events," saidChristopher Turner, M.D., Chief Medical Officer of Nuvalent. "These data highlight the potential for an ALK-selective inhibitor to broadly address medical needs for patients with ALK-positive solid tumors, and the importance of widespread genomic testing. We continue to enroll adult and adolescent TKI naïve and TKI pre-treated patients with advanced ALK-positive solid tumors beyond NSCLC in the global Phase 2 portion of our ALKOVE-1 study, and look forward to providing additional updates as these data mature."

Preliminary data are reported for 34 response-evaluable patients enrolled across 14 solid tumor types outside of NSCLC in the Phase 1 and Phase 2 portions of the ALKOVE-1 clinical trial as of a data cutoff date of August 7, 2025. The majority (32/34) of patients received the recommended Phase 2 dose of 150 mg once daily. Patients were ALK TKI-naïve (38%, 13/34) or ALK TKI pre-treated (62%, 21/34), and 62% (21/34) of patients had received prior chemotherapy.

Among all patients with advanced ALK-positive solid tumors treated with neladalkib, an objective response rate of 44% (15/34) was observed, including 9/13 patients who were ALK TKI-naïve and 6/21 who were ALK TKI pre-treated. 80% (12/15) of responders remained on treatment without disease progression as of the data cutoff date. Three case studies support neladalkib’s potential to induce deep and durable responses in a range of treatment settings:

Treatment ongoing for approximately 12 months with partial response in a TKI-naïve patient with an inflammatory myofibroblastic tumor previously treated with standard of care chemotherapy;
Treatment ongoing for approximately 16 months with partial response in a TKI and chemotherapy pre-treated patient with peritoneal mesothelioma; and,
Treatment ongoing for approximately 10 months with confirmed intracranial complete response in a TKI pre-treated patient with adenocarcinoma of unknown origin with baseline brain metastasis and ALK V1180L resistance mutation.
Among these 34 patients, neladalkib was generally well-tolerated with low rates of dose reduction (8.8%) and no discontinuations due to treatment-related adverse events as of the data cutoff date. The preliminary overall safety profile was consistent with its ALK-selective, TRK-sparing design, and with previously reported data.

Enrollment is ongoing in the global Phase 2 cohort of the ALKOVE-1 trial for adult and adolescent patients with advanced ALK-positive solid tumors other than NSCLC.

The company remains on track to report topline data for patients with TKI pre-treated ALK-positive NSCLC from the ALKOVE-1 trial by the end of 2025. Neladalkib is also being evaluated in ALKAZAR, a global Phase 3 randomized, controlled trial for the treatment of patients with TKI-naïve ALK-positive NSCLC.

About Neladalkib

Neladalkib is an investigational brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib 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/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.

(Press release, Nuvalent, OCT 18, 2025, View Source [SID1234656748])