ALK inhibitors(Anaplastic lymphoma kinase inhibitors), ROS1 inhibitors(Proto-oncogene tyrosine-protein kinase ROS inhibitors), TrkA antagonists(Nerve growth factor receptor Trk-A antagonists)

Therapeutic Areas

NeoplasmsRespiratory DiseasesNervous System Diseases+ [8]

Active Indication

Non-Small Cell Lung CancerReactive oxygen species 1 positive non-small cell lung cancerNTRK fusion-positive solid tumors+ [27]

Inactive Indication

Advanced breast cancerAdvanced Prostate CarcinomaAdvanced Sarcoma+ [10]

Originator Organization

Nerviano Medical Sciences S.r.l

Active Organization

Hoffmann-La Roche Ltd.

F. Hoffmann-La Roche Ltd.Hoffmann-La Roche, Inc.

+ [6]

Inactive Organization-

License Organization

Nerviano Medical Sciences S.r.l

Ignyta, Inc.

Drug Highest PhaseApproved

First Approval Date

Japan (18 Jun 2019),

NTRK fusion-positive solid tumors

RegulationBreakthrough Therapy (United States), Accelerated Approval (United States), Orphan Drug (United States), Priority Review (China), Orphan Drug (South Korea), Conditional marketing approval (China)

Structure/Sequence

Molecular FormulaC31H34F2N6O2

InChIKeyHAYYBYPASCDWEQ-UHFFFAOYSA-N

CAS Registry1108743-60-7

Clinical Trials associated with Entrectinib

NCT06528691

/ RecruitingPhase 2IIT

PHASE 2 Study of Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors (GLOBOTRK)

This clinical trial tests how well entrectinib works to treat patients less than 3 years of age with NTRK 1/2/3 or ROS1 fused, high grade glioma or other central nervous system (CNS) tumors.

Start Date01 May 2026

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

[+1]

CTR20253435

/ CompletedNot Applicable

评估受试制剂恩曲替尼胶囊与参比制剂恩曲替尼胶囊（罗圣全®）作用于健康成年受试者的餐后生物等效性研究

[Translation] A postprandial bioequivalence study evaluating the test formulation entrectinib capsules and the reference formulation entrectinib capsules (Luoshengquan®) in healthy adult subjects

主要研究目的研究餐后状态下单次口服受试制剂恩曲替尼胶囊与参比制剂恩曲替尼胶囊（罗圣全®）在健康成年受试者体内的药代动力学，评价餐后状态下口服两种制剂的生物等效性。次要研究目的研究受试制剂恩曲替尼胶囊和参比制剂“罗圣全®”在健康受试者中的安全性。

[Translation]

Primary Study Objectives To investigate the pharmacokinetics of the test formulation, entrectinib capsules, and the reference formulation, entrectinib capsules (Luoshengquan®), in healthy adult volunteers after a single oral dose in the fed state, and to evaluate the bioequivalence of the two formulations after oral administration in the fed state. Secondary Study Objectives To investigate the safety of the test formulation, entrectinib capsules, and the reference formulation, Luoshengquan®, in healthy volunteers.

Start Date15 Sep 2025

Sponsor / Collaborator

Qilu Pharmaceutica Hainanco Ltd.

CTR20253434

/ CompletedNot Applicable

评估受试制剂恩曲替尼胶囊与参比制剂恩曲替尼胶囊（罗圣全®）作用于健康成年受试者的空腹生物等效性研究

[Translation] A fasting bioequivalence study evaluating the test product entrectinib capsules and the reference product entrectinib capsules (Luoshengquan®) in healthy adult subjects

主要研究目的研究空腹状态下单次口服受试制剂恩曲替尼胶囊与参比制剂恩曲替尼胶囊（罗圣全®）在健康成年受试者体内的药代动力学，评价空腹状态下口服两种制剂的生物等效性。次要研究目的研究受试制剂恩曲替尼胶囊和参比制剂“罗圣全®”在健康受试者中的安全性。

[Translation]

Primary Study Objectives To investigate the pharmacokinetics of the test formulation, entrectinib capsules, and the reference formulation, entrectinib capsules (Luoshengquan®), in healthy adult volunteers after a single oral dose under fasting conditions, and to evaluate the oral bioequivalence of the two formulations under fasting conditions. Secondary Study Objectives To investigate the safety of the test formulation, entrectinib capsules, and the reference formulation, Luoshengquan®, in healthy volunteers.

Start Date12 Sep 2025

Sponsor / Collaborator

Qilu Pharmaceutica Hainanco Ltd.

100 Clinical Results associated with Entrectinib

100 Translational Medicine associated with Entrectinib

100 Patents (Medical) associated with Entrectinib

636

Literatures (Medical) associated with Entrectinib

01 Oct 2026·GENE

A systematic evaluation of the efficacy and safety of entrectinib in anaplastic thyroid carcinoma

Article

Author: Shen, Xiawei ; Jie, Ran

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with limited treatment options and poor responsiveness to conventional chemotherapy. In this study, we found that TrkA expression was markedly elevated in clinical ATC tissues compared with adjacent normal thyroid tissue. Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Consistently, the Trk inhibitor entrectinib decreased viability of genetically diverse ATC cell lines with nanomolar IC₅₀ values, and demonstrated synergy with paclitaxel across all tested lines. In vivo, entrectinib significantly delayed tumour progression in two independent xenograft studies, while combination therapy produced the most sustained suppression of tumour growth and the greatest extension of survival. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.

01 Sep 2026·LUNG CANCER

Comparative efficacy of taletrectinib versus first-generation TKIs in TKI-naïve ROS1+ non-small cell lung cancer: A matching-adjusted indirect comparison

Article

Author: Zhou, Caicun ; Chen, Wenfeng ; Liu, Geoffrey ; Pérol, Maurice ; Nagasaka, Misako ; Bazhenova, Lyudmila

BACKGROUND:

Taletrectinib is a next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) approved for the treatment of advanced ROS1+ non-small cell lung cancer (NSCLC). In the absence of head-to-head trials comparing ROS1 TKIs, we aimed to compare the efficacy of taletrectinib with first-generation TKIs, crizotinib and entrectinib, in TKI-naïve patients with ROS1+ NSCLC using an unanchored matching-adjusted indirect comparison.

METHODS:

Selected baseline covariates were used for adjustment between pooled taletrectinib data from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies and published data from the registrational crizotinib and entrectinib studies. A descriptive cross-trial comparison of safety for treatment-related adverse events (TRAEs) was also conducted.

RESULTS:

After adjustment for baseline covariates, taletrectinib was associated with significantly higher odds of objective response versus crizotinib or entrectinib, significantly longer duration of response versus entrectinib (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.21-0.60), significantly longer progression-free survival versus crizotinib (HR, 0.48; 95% CI, 0.27-0.88) or entrectinib (HR, 0.42; 95% CI, 0.27-0.65), and significantly longer overall survival versus crizotinib (HR, 0.34; 95% CI, 0.15-0.77) or entrectinib (HR, 0.48; 95% CI, 0.27-0.88). Results across sensitivity analyses consistently favored taletrectinib versus crizotinib or entrectinib. In a descriptive safety comparison, there were no marked differences in TRAE rates across taletrectinib, crizotinib, and entrectinib.

CONCLUSIONS:

In this analysis, taletrectinib was associated with more favorable response and survival outcomes compared with crizotinib or entrectinib in TKI-naïve patients with ROS1+ NSCLC after adjustment for baseline characteristics, supporting taletrectinib as an effective treatment option in this patient population.

01 Aug 2026·PATHOLOGY

Pathological correlates of response to short course neoadjuvant entrectinib in adult NTRK-rearranged spindle cell neoplasm

Letter

Author: Lee, Matilda ; Chua, Darren Yee Shuen ; Rasappan, Kumaran ; Jeyasekharan, Anand Devaprasath ; Chua, Zhengyu Samuel ; Mok, Yingting

News (Medical) associated with Entrectinib

16 Sep 2026

·www.globenewswire.com

Roche’s collaborator MediLink announces phase III data for Tam-Peli showing significantly improved overall survival in Chinese patient population with relapsed small-cell lung cancer

Roche’s collaborator MediLink announces phase III data for Tam-Peli showing significantly improved overall survival in Chinese patient population with relapsed small-cell lung cancer Tambotatug pelitecan (Tam-Peli) demonstrated statistically significant efficacy over topotecan in a phase III study conducted in China, reducing the risk of death by 54% and disease progression by 71%, while achieving an objective response rate of 59.1% vs 9.7%1 The novel B7-H3-targeted antibody-drug conjugate with a dual release mechanism of the payload is based on MediLink’s proprietary TMALIN® platform, designed to maximise antitumour activity while minimising off-target toxicity2,3 Roche is developing and commercialising Tam-Peli outside mainland China, Hong Kong, and Macau across multiple tumour types, with plans to rapidly initiate global trials Tam-Peli has received U.S. FDA and China CDE Breakthrough Therapy Designations for relapsed small-cell lung cancer (SCLC) 13 September 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) today announced that its collaborator MediLink released interim results from the randomised phase III TAISHAN-302 trial evaluating Tam-Peli (tambotatug pelitecan, YL201) versus topotecan in Chinese patients with relapsed small-cell lung cancer (SCLC) who progressed after prior platinum-based chemotherapy with or without a PD-L1 inhibitor.1 The trial met its primary endpoint of overall survival (OS) with Tam-Peli demonstrating a statistically significant and clinically meaningful OS benefit, reducing the risk of death by 54% (median OS 13.3 vs. 9.4 months; stratified HR=0.46; p<0.0001). Tam-Peli also showed robust efficacy across secondary endpoints, significantly extending progression-free survival (PFS) (median PFS 7.4 vs. 2.8 months) and response rates (59.1% vs. 9.7%) compared to standard-of-care topotecan.1 The trial results are being presented as a Late-Breaking Abstract during a Presidential Presentation at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul with simultaneous publication in The New England Journal of Medicine.1 Additionally, the Center of Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) for filing. “The second positive phase III trial for Tam-Peli, TAISHAN-302, reinforces our confidence in its potential to improve outcomes for people with cancer," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "These data demonstrate clinically meaningful survival and response rate improvements in an aggressive and hard-to-treat disease, supporting our plans to initiate global phase III trials quickly.” Consistent OS and PFS improvements were observed across prespecified subgroups, including age, chemotherapy-free interval (<90 vs. ≥90 days), and baseline liver or brain metastatic status. In patients with baseline brain metastases, Tam-Peli extended median intracranial PFS (6.1 months vs. 4.2 months; unstratified HR=0.43; 95% CI: 0.27–0.68) and achieved a higher intracranial response rate (32.4% vs. 2.9%).1 Tam-Peli showed a favourable and manageable safety profile, demonstrating lower rates of Grade ≥3 treatment-related adverse events (TRAEs) compared with topotecan (46.4% vs. 74.7%). Serious TRAEs occurred in 25.9% of patients receiving Tam-Peli versus 36.4% with topotecan. Treatment-emergent interstitial lung disease (ILD/pneumonitis) across all grades occurred in 4.9% of Tam-Peli patients versus 1.4% with topotecan; grade 3 ILD/pneumonitis events were low in both groups (0.9% each), with no Grade 4 or 5 events reported.1 Tam-Peli is designed to target B7-H3, a protein broadly expressed in solid tumours but minimally in normal tissue, allowing it to target cancer cells with high selectivity. Built on MediLink's TMALIN® platform, its stable linker and dual-release mechanism are designed to maximise therapeutic efficacy while limiting off-target toxicity.2,3 Following the positive phase III TAISHAN-301 trial (NCT06629597) in nasopharyngeal carcinoma, TAISHAN-302 represents the second positive phase III readout for Tam-Peli, conducted in patients in China. Under a collaboration and exclusive licensing agreement between Roche and MediLink Therapeutics, Roche holds development, manufacturing, and commercialisation rights for Tam-Peli worldwide, outside mainland China, Hong Kong, and Macau. Roche is advancing clinical development in its licensed territories across multiple solid tumour types and plans to rapidly initiate global phase III trials. TAISHAN-302 (NCT06612151) is a randomised, open-label phase III study evaluating the efficacy and safety of Tam-Peli (2.0 mg/kg intravenously on day 1 of each 21-day cycle, maximum dose 200 mg) compared with topotecan in patients with small-cell lung cancer (SCLC) who have progressed after one prior line of platinum-based chemotherapy with or without a PD-L1 inhibitor. The trial enrolled 451 patients across 85 study sites in China. The primary endpoint of the trial is overall survival (OS). Key secondary endpoints include investigator-assessed progression-free survival (PFS) and objective response rate (ORR), alongside disease control rate (DCR), duration of response (DoR), time to response (TTR), safety, pharmacokinetics, and immunogenicity.1 Tambotatug pelitecan (Tam-Peli; YL201) is an investigational antibody-drug conjugate (ADC) targeting B7-H3, a protein highly expressed across various solid tumours, both on the tumour cells and in the microenvironment, but limited in healthy tissues.1,2 Utilising MediLink Therapeutics’ TMALIN® (Tumour Microenvironment-Activatable Linker) platform, Tam-Peli links a B7-H3-specific monoclonal antibody to a novel topoisomerase 1 inhibitor payload with a drug-to-antibody ratio (DAR) of 8. By combining a stable, hydrophilic linker with a dual-release mechanism, Tam-Peli is designed to deliver its cytotoxic payload both inside tumour cells as well as extracellularly in the tumour microenvironment, maximising therapeutic efficacy while minimising systemic toxicity.2,3 Beyond SCLC, Tam-peli holds two U.S. Food and Drug Administration (FDA) Orphan Drug Designations and three China Center of Drug Evaluation (CDE) Breakthrough Therapy Designations (BTDs) across additional indications, including nasopharyngeal carcinoma (NPC), esophageal squamous cell carcinoma (ESCC), and pancreatic cancer. In January 2026, Roche entered into an exclusive licensing agreement with MediLink Therapeutics for the development, manufacturing, and commercialisation of Tam-Peli worldwide, excluding mainland China, Hong Kong SAR and Macau. Lung cancer remains the leading cause of cancer-related deaths worldwide, surpassing the combined mortality rates of breast, prostate, and stomach cancers. Each year, it claims the lives of 1.8 million people. SCLC accounts for 15% of lung cancer diagnoses.4 It is a highly aggressive form of lung cancer which progresses rapidly, regardless of the stage of disease at diagnosis. Despite advances in first-line treatment, SCLC frequently relapses or progresses and outcomes remain poor for many people with recurrent disease, highlighting the continued need for more effective treatment options. Roche is committed to advancing the field of lung cancer treatments, leveraging more than 20 years of scientific expertise to improve patient outcomes. Roche’s 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. 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. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market. References [1] Zhang L, Zhao Y, Liu H, et al. Tam-Peli, an Anti-B7-H3 Antibody-Drug Conjugate, Versus Topotecan in Relapsed SCLC: A Randomized, Open-Label, Phase 3 Study (TAISHAN-302). WCLC 2026: Abstract PL02.03. [2] Xu J, et al. Cancer Res. 2023;83:6304. [3] Ma Y, et al. Nat Med. 2025;31:1949-1957. [4] Rudin CM, et al. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. The content above comes from the network. if any infringement, please contact us to modify.

License out/inClinical ResultBreakthrough TherapyOrphan Drug

14 Sep 2026

·allsci.com

Cardiff and Nerviano settle onvansertib license dispute ahead of planned Phase III trial

Cardiff Oncology (Nasdaq: CRDF) and Italy-based Nerviano Medical Sciences S.r.l. (NMS) have settled their litigation and amended their 2017 exclusive license agreement covering global rights to onvansertib, an oral polo-like kinase 1 (PLK1) inhibitor that Cardiff is preparing to advance into a registrational Phase III trial in first-line RAS-mutated metastatic colorectal cancer (mCRC). The amendment resolves all outstanding disputes between the two companies, with both parties agreeing to a mutual release of claims and a joint request to dismiss pending litigation in the US District Court for the Southern District of California with prejudice. The dispute arose after NMS notified Cardiff in February 2026 that it believed the company had materially breached the license agreement by declining to name an NMS employee as a joint inventor on two US patents. Cardiff filed suit on May 19 seeking injunctive and declaratory relief, and NMS subsequently issued a notice on May 27 purporting to terminate the agreement, also alleging that Cardiff had failed to use commercially reasonable efforts to advance onvansertib. The amendment gives NMS a more formal role in onvansertib's late-stage development through a board observer position, participation in Cardiff's Scientific Advisory Board, and development objectives tied to the planned Phase III program. Cardiff retains global development and commercialization rights, while the revised agreement clarifies and expands the royalty framework. The original 2017 agreement provided for Cardiff to pay development milestones of up to an aggregate of USD 15 million, commercial milestones, and royalties based on sales volume, according to Cardiff's public filings. Granting a licensor board observer and Scientific Advisory Board access is structurally uncommon in standard exclusive license agreements and is more typical of equity investor or strategic co-development relationships. The arrangement gives NMS visibility into Cardiff's Phase III planning without transferring equity or altering the fundamental rights structure. NMS's institutional interest in preserving its downstream royalty position — consistent with its history of out-licensing kinase inhibitor intellectual property, including the enabling chemistry behind encorafenib and entrectinib — provides context for the settlement terms. The timing follows a period of positive clinical momentum for onvansertib. Cardiff reported Phase II CRDF-004 data at ASCO 2026 showing a 72.2% overall response rate and a progression-free survival hazard ratio of 0.37 versus combined standard of care in first-line RAS-mutated mCRC. Cardiff also completed a successful End-of-Phase 2 meeting with the FDA and selected the 30 mg dose of onvansertib in combination with FOLFIRI/bevacizumab for the registrational program. Cardiff's new leadership team — CEO Mani Mohindru and a newly appointed CFO and COO installed in April 2026 — resolved the NMS dispute within approximately five months of taking office. Cardiff raised USD 10 million in a registered direct offering in July 2026 ahead of the Phase III initiation. The next meaningful milestone is the launch of that registrational trial in first-line RAS-mutated mCRC, which both Cardiff and NMS said they plan to advance jointly. Spot something wrong? Report an issue with this article

Phase 2Phase 3License out/inExecutive ChangeClinical Trial Failure

09 Sep 2026

·www.biospace.com

Callio Therapeutics Appoints Zachary Hornby as Chief Executive Officer

Veteran biotech executive to lead company growth as it advances multiple dual-payload ADCs through clinical development for people living with cancer Piers Ingram, PhD, Co-Founder, transitions to Senior Advisor and continues to serve on the Board of Directors; Jerome Boyd-Kirkup, PhD, founding Chief Scientific Officer, transitions to Senior Scientific Advisor SAN DIEGO and SEATTLE and SINGAPORE, Sept. 09, 2026 (GLOBE NEWSWIRE) -- Callio Therapeutics (“Callio” or “the Company”), a clinical-stage biotechnology company advancing dual-payload antibody-drug conjugates (ADCs) as the next frontier of rationally designed targeted cancer therapy, today announced the appointment of Zachary (“Zach”) Hornby as Chief Executive Officer. Hornby brings significant experience leading innovative biotechnology companies through clinical development, private and public financings, and strategic partnerships. Hornby has served in executive and director roles across multiple public and private biotechnology companies. He was most recently CEO, President, and a Director at Boundless Bio (Nasdaq: BOLD), a precision oncology company that raised $350 million in private and public capital and advanced three internally discovered molecules into clinical development. Previously, Hornby held Chief Financial Officer and Chief Operating Officer roles at Ignyta, where he helped lead the company's IPO, oversaw its development portfolio, was the team leader for cancer drug Rozlytrek™, and led the business development process behind its $2 billion acquisition by Roche. He currently serves as a Director at Radionetics Oncology and Telperian, Inc. Hornby holds BS and MS degrees in biology from Stanford University and an MBA from Harvard Business School. "Resistance is the defining challenge facing ADCs today, and Callio's leading approach in the emerging dual-payload space tackles resistance head-on with rational combination payloads delivered in a tumor-specific manner," said Hornby. "With CLIO-8221 in the clinic and additional programs advancing toward the clinic in the near future, I look forward to building on the strong scientific foundation to deliver meaningful impact for patients and shareholders." As part of the leadership transition, Piers Ingram, PhD, Callio’s founding CEO, will transition to a Senior Advisor role and continue to serve on Callio’s Board of Directors, ensuring continuity of the company's foundational scientific and strategic leadership. Jerome Boyd-Kirkup, PhD, Callio’s founding Chief Scientific Officer, will transition to a Senior Scientific Advisor role. The leadership transition reflects Callio’s corporate evolution as it advances its pipeline, including its lead clinical program, CLIO-8221, and expands the global impact of its leading dual-payload ADC platform. Ingram will continue to lead Hummingbird Bioscience (“Hummingbird”), from which Callio exclusively licensed its multi-payload ADC platform in oncology and associated intellectual property and pipeline assets in 2025, as its CEO, and Boyd-Kirkup will continue to serve Hummingbird as its CSO. "Callio has entered an exciting stage as we advance CLIO-8221 through a Phase 1 clinical trial and broaden the reach of our dual-payload ADC platform across a growing pipeline," said Ingram. "Zach's track record of leading clinical-stage companies through drug development, global registrations, and capital raising makes him the right person to guide Callio forward in this next chapter and beyond. Through a collaborative development agreement, Hummingbird will continue to provide research and development support to Callio via Hummingbird’s expertise and AI-first approach to ADC discovery. I will continue to partner with the Callio team to advance dual-payload ADCs and deliver the next generation of ADC medicines for patients." About Callio Therapeutics Callio Therapeutics is a clinical-stage biotechnology company that is developing dual-payload antibody-drug conjugates (ADCs) as the next frontier of targeted cancer therapy to address high incidence tumors where better therapies are needed. Its proprietary platform pairs modular, adaptable linker technology with rationally selected synergistic payload combinations designed to block key resistance mechanisms that enable cancer’s escape. The Company’s lead clinical program, CLIO-8221, is a HER2-targeted dual-payload ADC with potential to prevent and overcome treatment resistance that limits efficacy of current ADCs. Located in San Diego, Seattle, and Singapore, backed by top life science investors, and led by an experienced team with a track record of ADC development and oncology drug approvals, Callio Therapeutics is built to deliver the next generation of dual-payload ADCs and better outcomes for people living with cancer. For more information, visit and follow Callio Therapeutics on LinkedIn . About CLIO-8221 HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating clinical benefit across tumor types. However, most patients eventually progress on treatment despite their tumors retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key driver of treatment failure. CLIO-8221 is a novel, first-in-class, dual-payload ADC targeting HER2, designed to overcome emergent resistance. CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and further sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients with HER2-expressing tumors. CLIO-8221 is currently being evaluated in an ongoing Phase 1/2, first-in-human, dose-escalation and expansion study in adult patients with metastatic or unresectable HER2-expressing solid tumors, including those who previously received trastuzumab deruxtecan (T-DXd). The first patient was dosed in March 2026, and enrollment is ongoing in Australia and the US, with plans to open the study in China ( NCT07300943 ). Contacts Media: Jeremy Sauer media@calliotx.com Ally Stubin – ICR Healthcare Ally.Stubin@ICRHealthcare.com (646) 667-1861 Investors: ir@calliotx.com Stephanie Carrington – ICR Healthcare stephanie.carrington@ICRHealthcare.com (646) 277-1282

Executive ChangePhase 1ADCIPO

100 Deals associated with Entrectinib

External Link

KEGG	Wiki	ATC	Drug Bank
D10926	Entrectinib	L01XE56	DB11986

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	South Korea	Roche Holding AG	21 Apr 2020
Reactive oxygen species 1 positive non-small cell lung cancer	United States	Genentech, Inc.	15 Aug 2019
NTRK fusion-positive solid tumors	Japan	Chugai Pharmaceutical Co., Ltd.	18 Jun 2019

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Brain Cancer	NDA/BLA	China	Roche Holding AG	29 Oct 2021
Glioma	Phase 3	United Kingdom	-	30 Nov 2025
Hematologic Neoplasms	Phase 3	United Kingdom	-	30 Nov 2025
Lymphoproliferative Disorders	Phase 3	United Kingdom	-	30 Nov 2025
Melanoma	Phase 3	United Kingdom	-	30 Nov 2025
ROS1 fusion positive Neoplasms	Phase 3	United Kingdom	-	30 Nov 2025
ALK positive Non-Small Cell Lung Cancer	Phase 3	United States	F. Hoffmann-La Roche Ltd.	11 Jan 2023
ALK positive Non-Small Cell Lung Cancer	Phase 3	China	F. Hoffmann-La Roche Ltd.	11 Jan 2023
ALK positive Non-Small Cell Lung Cancer	Phase 3	Japan	F. Hoffmann-La Roche Ltd.	11 Jan 2023
ALK positive Non-Small Cell Lung Cancer	Phase 3	Australia	F. Hoffmann-La Roche Ltd.	11 Jan 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


WCLC2026	Not Applicable	ROS1 fusion positive Neoplasms First line MET protein expression	19	Entrectinib (MET-positive)	wzajawbhmn(ahmfxkaayj) = ywzlbqyzwe papodqhqhk (yiwrfaeiup ) View more	Negative	12 Sep 2026
				Entrectinib (MET-negative)	wzajawbhmn(ahmfxkaayj) = gvshlegnqd papodqhqhk (yiwrfaeiup ) View more
NCT04302025 (NAUTIKA1, WCLC2026)	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant ROS1+ \| NTRK+ \| PD-L1+	15	Entrectinib	bmrqctxlqm(dvkiwcials) = bdplaetief vlrtdetlks (kdgnikvlnf ) View more	Positive	12 Sep 2026
				Entrectinib (NTRK+ NSCLC)	bmrqctxlqm(dvkiwcials) = guzxgyolyb vlrtdetlks (kdgnikvlnf ) View more
ESMO_SRC2026	Not Applicable	NTRK fusion-positive solid tumors NTRK fusion-positive	461	Entrectinib	qhjszarbjr(dprizmoazc) = 23% hvdpqzjjcv (gtitrkeqbs ) View more	Positive	09 Mar 2026
SNO2025	Not Applicable	Astrocytoma BRAF V600E mutation \| CDKN2A deletion \| receptor tyrosine-kinase (RTK) genes rearrangements	42	dabrafenib + trametinib	cqzoqaoqpj(ruxususncj) = CDKN2A deletions were uniformly distributed between BRAF-mutated and RTK-fused cases lkojujpfbx (lfzaafjwar ) View more	Positive	19 Nov 2025
				entrectinib
ESMO2025	Not Applicable	Glioblastoma BRAFV600E mutation \| NRTK-fusion	25	Dabrafenib-trametinib	nlrjvixvbv(njtowkltya) = qzizejoajq mxtnuuwrtq (zjrrnqmvuw ) View more	Positive	17 Oct 2025
				Larotrectinib	nlrjvixvbv(njtowkltya) = jwmnrhdpbx mxtnuuwrtq (zjrrnqmvuw ) View more
EANO2025	Not Applicable	Recurrent Malignant Glioma BRAFV600E mutation \| NRTK-fusion	25	Dabrafenib-trametinib	yfcbyroekn(jzalemkpml) = undyiebype pgzncewkbk (gvtvkmnenk ) View more	Positive	16 Oct 2025
				Larotrectinib	lzqehjhmat(xpnxsbwwoc) = zatawpfvsq mhqvevyypb (iplencvrfe ) View more
SGO2025	Not Applicable	Female Genital Neoplasms tumor-agnostic	1,016	Pembrolizumab	eyelshkzyr(bgyhgrgkep) = gdkizratct dchdkyklpi (brjwipixza )	Positive	01 Sep 2025
				Dostarlimab	cyazhgqtka(cehpsretup) = jqyjggmxhi xafkwplkis (bpznwfsoac )
NCT02650401; NCT04589845; NCT02568267 (ASCO2025)	Not Applicable	-	113	Entrectinib	sjsfmzxbbp(cginyxutos) = jwaygorofl vkevnuieby (uarlslrwmi, 48.2 - 85.7) View more	Positive	30 May 2025
NCT02568267 \| NCT02650401 \| NCT04589845 (STARTRK-NG, TAPISTRY, STARTRK-2, Pubmed \| Eur J Cancer)	Not Applicable	NTRK fusion-positive Central Nervous System Neoplasms NTRK \| ROS1	91	Entrectinib	fnhmezveak(bcxgheshbu) = lkxggdfump pzxvfwrywk (lhvpfrgann, 57.2 - 85.0) View more	Positive	01 May 2025
				Placebo	fnhmezveak(bcxgheshbu) = yeroazcvan pzxvfwrywk (lhvpfrgann, 40.8 - 84.6) View more
NCT05396859 (ASH2024)	Phase 1	Acute Myeloid Leukemia	-	Entrectinib	rjbtnvhpga(tkurtzanuq) = 50% had grade 3+ treatment-related AEs, with 5 having grade 3 febrile neutropenia (4 of whom had active disease at time of onset) koprznjyzn (jhoezhoyzf ) View more	-	07 Dec 2024

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis