CLINICAL TRIALS PROFILE FOR REPOTRECTINIB

All Clinical Trials for Repotrectinib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03093116 ↗	A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements	Recruiting	TP Therapeutics, Inc.	Phase 1/Phase 2	2017-02-27	Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
NCT03093116 ↗	A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements	Recruiting	Turning Point Therapeutics, Inc.	Phase 1/Phase 2	2017-02-27	Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
NCT04094610 ↗	A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations	Recruiting	Turning Point Therapeutics, Inc.	Phase 1/Phase 2	2020-03-20	Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.
NCT04772235 ↗	Phase I Study of Repotrectinib and Osimertinib in NSCLC Patients	Not yet recruiting	Turning Point Therapeutics, Inc.	Phase 1	2021-04-01	This is a Phase I study of repotrectinib in combination with osimertinib in patients with advanced or metastatic EGFR mutant non small cell lung cancer (NSCLC). The study will be conducted in 2 parts, Part Ia and Part Ib, and its purpose will be to find the incidence of dose-limiting toxicities (DLTs) as defined by the primary safety and tolerability endpoint. The Phase Ia study will also determine the impact of repotrectinib on osimertinib pharmacokinetics (PK) and the maximum tolerated dose (MTD), if reached, of repotrectinib given in combination with osimertinib and the recommended Phase II dose (RP2D). Dose escalation will be conducted according to a 'Rolling-6' based study design with 3 dose levels for repotrectinib: 80 mg once a day (QD), 160 mg QD or 160 mf QD during 14 days followed by 160 mg twice a day (BID); in combination with 80 mg QD of osimertinib. A total of 6 patients will be enrolled in each dose level cohort. In addition, this Phase Ib study will test early drug activity (efficacy) of the proposed combination treatment in an expansion cohort at the RP2D.
NCT04772235 ↗	Phase I Study of Repotrectinib and Osimertinib in NSCLC Patients	Not yet recruiting	Instituto Oncológico Dr Rosell	Phase 1	2021-04-01	This is a Phase I study of repotrectinib in combination with osimertinib in patients with advanced or metastatic EGFR mutant non small cell lung cancer (NSCLC). The study will be conducted in 2 parts, Part Ia and Part Ib, and its purpose will be to find the incidence of dose-limiting toxicities (DLTs) as defined by the primary safety and tolerability endpoint. The Phase Ia study will also determine the impact of repotrectinib on osimertinib pharmacokinetics (PK) and the maximum tolerated dose (MTD), if reached, of repotrectinib given in combination with osimertinib and the recommended Phase II dose (RP2D). Dose escalation will be conducted according to a 'Rolling-6' based study design with 3 dose levels for repotrectinib: 80 mg once a day (QD), 160 mg QD or 160 mf QD during 14 days followed by 160 mg twice a day (BID); in combination with 80 mg QD of osimertinib. A total of 6 patients will be enrolled in each dose level cohort. In addition, this Phase Ib study will test early drug activity (efficacy) of the proposed combination treatment in an expansion cohort at the RP2D.
NCT05004116 ↗	A Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer	Recruiting	Memorial Sloan Kettering Cancer Center	Phase 1/Phase 2	2021-08-09	This study will test the safety of the study drug, repotrectinib, in combination with chemotherapy (irinotecan and temozolomide) in children and young adults who have advanced or metastatic solid tumors. We researchers will try to find the highest dose of the study drug that causes few or mild side effects in study participants. When the researchers find this dose, we will evaluate it in a different group of participants to find out whether repotrectinib in combination with chemotherapy is an effective treatment for children and young adults who have advanced/metastatic solid tumors. Another purpose of the study is to look at the way the body absorbs, distributes, and gets rid of repotrectinib.

Clinical Trial Conditions for Repotrectinib

Condition Name

Condition Name for Repotrectinib
Intervention	Trials
Metastatic Solid Tumor	4
Locally Advanced Solid Tumors	2
Advanced Solid Tumor	2
Metastatic Solid Tumors	2

Condition MeSH

Condition MeSH for Repotrectinib
Intervention	Trials
Neoplasms	6
Carcinoma, Non-Small-Cell Lung	4
Lymphoma, Follicular	1
Lymphoma, Non-Hodgkin	1

Clinical Trial Locations for Repotrectinib

Trials by Country

Trials by Country for Repotrectinib
Location	Trials
United States	55
China	38
Spain	14
France	12
Japan	9

Trials by US State

Trials by US State for Repotrectinib
Location	Trials
Texas	5
Florida	4
Ohio	4
New York	4
Colorado	3

Clinical Trial Progress for Repotrectinib

Clinical Trial Phase

Clinical Trial Phase for Repotrectinib
Clinical Trial Phase	Trials
PHASE2	3
PHASE1	2
Phase 3	1

Clinical Trial Status

Clinical Trial Status for Repotrectinib
Clinical Trial Phase	Trials
Recruiting	11
COMPLETED	1
Not yet recruiting	1

Clinical Trial Sponsors for Repotrectinib

Sponsor Name

Sponsor Name for Repotrectinib
Sponsor	Trials
Turning Point Therapeutics, Inc.	6
Bristol-Myers Squibb	3
Groupe Francais De Pneumo-Cancerologie	1

Sponsor Type

Sponsor Type for Repotrectinib
Sponsor	Trials
Industry	11
Other	8

Repotrectinib: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 30, 2025

Introduction

Repotrectinib, a next-generation ROS1/TRK kinase inhibitor, has emerged as a promising candidate in the targeted oncology therapeutics landscape. Developed by Turning Point Therapeutics, Inc., it is designed to overcome resistance mechanisms encountered with earlier-generation kinase inhibitors. As the oncology market evolves rapidly, understanding the current clinical trial landscape, market potential, and future growth projections for Repotrectinib becomes vital for stakeholders, including investors, healthcare providers, and pharmaceutical companies.

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Clinical Trials Update

Current Status and Ongoing Studies

Repotrectinib has demonstrated notable activity against ROS1 fusion-positive non-small cell lung cancer (NSCLC) and TRK fusion-positive tumors. The compound has progressed through early-phase trials, with Phase 1 and Phase 2 studies highlighting its safety profile and efficacy.

• Phase 1/2 TRIDENT-1 Trials: Turning Point's pivotal trial, TRIDENT-1, is a multi-cohort study evaluating Repotrectinib across various tumor types, notably ROS1-positive NSCLC, TRK fusion cancers, and other solid tumors. As of late 2022, preliminary data indicates significant intracranial and systemic responses, notably in patients previously treated with other TKIs.

• Efficacy in TKI-Resistant Settings: In ROS1-positive NSCLC patients resistant to crizotinib and entrectinib, Repotrectinib has shown promising activity, with objective response rates (ORR) exceeding 50% in select cohorts [1].

• Intracranial Activity: Given its CNS penetrance, the drug demonstrates substantial intracranial responses, a crucial advantage over earlier therapies, especially considering the propensity for brain metastases in ROS1 and TRK fusion-positive cancers.

Safety and Tolerability

Clinical data underscores a manageable safety profile. Common adverse events include fatigue, elevated liver enzymes, and gastrointestinal symptoms, aligning with other kinase inhibitors. Importantly, the drug exhibits minimal off-target effects and limited severe adverse events, bolstering its potential for broader patient use.

Regulatory Status and Future Trials

Turning Point has submitted data to regulatory agencies, with discussions underway for potential accelerated approval pathways, especially in populations with limited treatment options. Upcoming trials aim to expand into pediatric indications and additional tumor types exhibiting NTRK fusions.

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Market Analysis

Market Overview

The targeted oncology therapeutics market, particularly for kinase inhibitors, is projected to grow substantially. Key drivers include the increasing precision medicine paradigm, rising prevalence of ROS1 and TRK fusion-positive cancers, and unmet medical needs.

• ROS1-positive NSCLC: Estimated to constitute approximately 1-2% of NSCLC cases, translating to approximately 20,000 new cases annually in the U.S. alone [2].
• NTRK Fusion Cancers: Although rare (~0.1% of solid tumors), NTRK gene fusions are widespread across tumor types, providing a broad potential market.

Competitive Landscape

Repotrectinib faces competition from established therapies:

• Crizotinib and Entrectinib: First-generation ROS1 and TRK inhibitors with proven efficacy but limited CNS penetration and resistance issues.
• Lorlatinib: Administered for ROS1-positive NSCLC, but with notable neurotoxicity concerns.

Emerging competitors include Taletrectinib and Entrectinib in clinical development, focusing on resistance and CNS activity.

Market Penetration Potential

Repotrectinib's efficacy against resistance mutations and CNS disease positions it favorably. It could capture significant market share, particularly among patients with resistance to first-line TKIs and CNS metastases.

Pricing and Reimbursement Outlook

Given the targeted nature, similar drugs are priced in the $10,000–$15,000/month range. Reimbursement will hinge on confirmed efficacy, safety, and clinical benefit over existing options, influencing adoption rates.

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Future Projections and Growth Drivers

Market Expansion Forecast

• Early Dominance (Next 2-3 years): Initial approval in ROS1-positive NSCLC for patients resistant to existing TKIs.
• Long-term Growth (3-7 years): Potential expansion into broader adult and pediatric cancers with NTRK fusions, leveraging high intracranial activity.

Market analysts project that Repotrectinib could reach a peak global sales of $1.2 billion by 2030, contingent on successful regulatory approvals and competitive positioning [3].

Factors Supporting Growth

• CNS Efficacy: Differentiates Repotrectinib, especially in patients with brain metastasis.
• Resistance Overcoming Ability: Targets mutations like G2032R, a common cause of TKI resistance.
• Patient Population Size: Even though the NTRK fusion-positive population is small, its broad tumor distribution offers therapeutic versatility.
• Expanding Indications: Pediatric brain tumors and other solid tumors harboring NTRK fusions present expansion opportunities.

Challenges and Risks

• Regulatory Hurdles: Accelerated approval pathways are subject to evolving regulatory landscapes.
• Competitive Dynamics: Superior efficacy or safety profiles by competitors could impact market share.
• Resistance Mechanisms: Tumor heterogeneity might necessitate combination therapies in future.

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Conclusion

Repotrectinib has demonstrated compelling clinical activity in early trials, especially in TKI-resistant ROS1- and TRK-fusion-positive cancers, with notable intracranial response profiles. Its unique features forecast a significant impact within a niche yet expanding market, provided ongoing trials confirm efficacy and safety. Strategic positioning in pipeline development and regulatory engagement will be critical for maximizing its future commercial potential.

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Key Takeaways

• Clinical Progress: Repotrectinib is in pivotal trial stages, showing promising efficacy in resistant NSCLC and NTRK fusion-positive tumors, including intracranial activity.
• Market Opportunity: Targeted oncology markets, especially for ROS1 and NTRK fusions, are expanding, with Repotrectinib positioned to address unmet needs, notably in CNS metastases.
• Growth Potential: Estimated to reach $1.2 billion globally by 2030, driven by resistance management and indication expansion.
• Competitive Edge: CNS penetrance and resistance mutation activity distinguish Repotrectinib from earlier TKIs.
• Challenges: Regulatory pathways, competition, and tumor heterogeneity remain hurdles for commercialization.

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FAQs

1. When is Repotrectinib expected to receive regulatory approval?
   While ongoing data reviews are promising, regulatory approval timelines depend on definitive trial outcomes, which could occur within 1-2 years. Accelerated pathways may expedite earliest market entry.

2. What makes Repotrectinib different from existing ROS1/TRK inhibitors?
   Its ability to overcome resistance mutations and penetrate the central nervous system makes Repotretinib favorable for patients with brain metastases or resistant tumors.

3. Which patient populations are most likely to benefit from Repotrectinib?
   Patients with ROS1-positive NSCLC resistant to initial TKIs and those with NTRK fusion-positive solid tumors, especially with CNS metastases, stand to benefit most.

4. What are the primary safety concerns associated with Repotrectinib?
   Clinical trial data indicate manageable safety with fatigue, liver enzyme elevations, and gastrointestinal effects as common adverse events.

5. How might Repotrectinib impact the landscape of targeted oncology therapeutics?
   Its capacity to address resistance and CNS disease could establish it as a cornerstone in precision cancer therapy, influencing treatment algorithms and future drug development.

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References

[1] Turning Point Therapeutics, "TRIDENT-1 Trial Data," 2022.

[2] American Cancer Society, "Non-Small Cell Lung Cancer Facts & Figures," 2021.

[3] MarketWatch, "Oncology Drugs Market Forecast," 2022.