Augtyro (repotrectinib) / ZAI Lab, BMS - LARVOL DELTA

Repotrectinib in Patients With ROS1 Fusion-Positive (ROS1+) NSCLC: Long-Term Follow-Up From the Phase 1/2 TRIDENT-1 Trial (IASLC-WCLC 2025) - P1/2 | "Conclusions : Repotrectinib continued to demonstrate durable efficacy and intracranial activity in patients with ROS1 + NSCLC in the TKI-naïve and the 1 prior TKI and no chemo cohorts of TRIDENT-1, with median follow-up of ≥42 months. Safety outcomes were consistent with previous reports."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Pediatrics • Solid Tumor • NTRK • ROS1

Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 ."

Journal • P1/2 data • Oncology • Solid Tumor • NTRK • ROS1

From class effects to specificity FAERS evidence and network mapping of adverse events in NSCLC targeted therapy. (PubMed, Int J Surg) - "This first NSCLC-focused FAERS comparison integrating four-method signal detection with network analysis delineates reproducible class effects superimposed by drug-specific toxicities. Findings support tailored monitoring (e.g., dermatologic care for EGFR-TKIs; ECG/electrolytes for osimertinib; lipid/CK surveillance for ALK-TKIs; blood pressure/liver testing for RET-TKIs) to inform risk-aware first-line decisions."

Adverse events • Journal • Cardiovascular • Dyslipidemia • Hypertension • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

Reporos trial-GFPC 04-2023: Open-label phase II efficacy study of repotrectinib in frail patients with ROS1-rearranged metastatic NSCLC (ESMO 2025) - P2 | "Background ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. As of April 15, 2025, 7 patients have been included in the study. This trial receives financial support and drug supply (REPROTECTINIB) from BMS, which is not involved in the design and conduct of the study, nor in the collection, management, analysis, or interpretation of the data."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

Partial Response to Repotrectinib in ROS1-Rearranged Lung Squamous Cell Carcinoma: A Brief Report. (PubMed, Clin Lung Cancer) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ROS1

Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+ NSCLC (IASLC-WCLC 2025) - P1/2 | "50% of patients received ≥2 (range 1-4) prior ROS1 TKIs, of whom 93% had prior lorlatinib, repotrectinib, and/or taletrectinib. In this pivotal ROS1 TKI pre-treated data set, zidesamtinib demonstrated clinically meaningful activity and durability, including in patients with CNS disease and/or ROS1 G2032R-mutations, and/or in patients who had exhausted available options. Encouraging preliminary activity was also observed in TKI-naïve patients. Zidesamtinib's safety profile was consistent with its highly ROS1-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Solid Tumor • ROS1

Neurological adverse events of ROS1 inhibitors for non-small cell lung cancer: data from the FDA adverse event reporting system. (PubMed, Front Neurol) - "Although agents such as Crizotinib, Ceritinib, Lorlatinib, Entrectinib, and Repotrectinib have demonstrated strong efficacy and intracranial activity, their neurological safety profiles remain insufficiently characterized in real-world settings. This study provides real-world evidence that newer ROS1 inhibitors exhibit earlier but generally manageable neurological AEs. Clinicians should implement early neurotoxicity monitoring and individualized risk assessment to ensure safe and effective targeted therapy for ROS1-positive NSCLC."

Adverse events • Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase I/II ARROS-1 study of zidesamtinib (NVL-520) in ROS1 fusion-positive solid tumours (ESMO 2024) - P1/2 | "Pts had a median of 3 (range: 1-11) prior anticancer therapies, including any ROS1 TKI (99%); lorlatinib (55%), repotrectinib (repo; 21%), or either (67%); ≥2 ROS1 TKIs (69%); and chemo (66%). Zidesamtinib demonstrated encouraging efficacy and durability in pts with pretreated ROS1+ NSCLC, including those who had exhausted available therapies, with ROS1 resistance mutations including G2032R, and/or with CNS mets. Safety was favorable and consistent with the highly ROS1-selective and TRK-sparing design. Ph 2 enrollment is ongoing with registrational intent in pts with TKI-naïve and pretreated ROS1+ NSCLC."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Repotrectinib in tyrosine kinase inhibitor (TKI)-naïve patients (pts) with advanced ROS1 fusion-positive (ROS1+) NSCLC in the phase 1/2 TRIDENT-1 trial: Clinical update, treatment beyond progression and subsequent therapies. (ASCO 2024) - P1/2 | "With a median follow-up of ~3 years in TRIDENT-1, repotrectinib continued to demonstrate durable clinical activity in ROS1 TKI-naïve pts. Progression patterns and treatment beyond progression were described for the first time."

Clinical • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Pivotal Data Update from the Phase 1/2 TRIDENT-1 Trial of Repotrectinib in Patients with ROS1+ Advanced Non-Small Cell Lung Cancer (NSCLC) (IASLC-TTLC 2023) - P1/2 | "With a longer follow-up, repotrectinib remains well tolerated with a manageable safety profile. Efficacy and safety were generally consistent across age subgroups."

Clinical • Metastases • P1/2 data • Anemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • ROS1

Repotrectinib in Patients with ROS1 Fusion-positive (ROS1+) NSCLC: Update from the Pivotal Phase 1/2 TRIDENT-1 Trial (IASLC-WCLC 2023) - P1/2 | "With 14 months' minimum follow-up in TRIDENT-1, repotrectinib continued to demonstrate durable efficacy in patients with ROS1+ NSCLC, including intracranial activity, in both TKI-naïve and 1 prior TKI and no chemo cohorts. Safety in patients treated at RP2D was manageable, consistent with previous reports in all treated patients."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - P1/2 | "Repotrectinib had durable clinical activity in patients with ROS1 fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

FDA Approval Summary: Repotrectinib for locally advanced or metastatic ROS1-positive non-small cell lung cancer. (PubMed, Clin Cancer Res) - P1/2 | "The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs."

FDA event • Journal • Metastases • Ataxia • CNS Disorders • Cognitive Disorders • Constipation • Developmental Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor • ROS1

Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC) (AACR-NCI-EORTC 2022) - P1/2 | "He played a monumental role in developing repotrectinib, lazertinib, amivantamab, and other targeted- and immuno-therapies, many of which were acknowledged for breakthrough therapy designation and FDA approval. Repotrectinib achieves durable activity, including intracranial responses, in TKI-naïve and TKI-pretreated patients with ROS1+ advanced NSCLC, and those with ROS1 G2032R. Repotrectinib safety is well characterized, manageable, and compatible with long-term use."

Clinical • Late-breaking abstract • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1. (ASCO 2023) - P1/2 | "In TRIDENT-1, repotrectinib showed durable clinical activity in ROS1 TKI-naïve and -pretreated pts with or without BL CNS mets, including intracranial responses. Repotrectinib safety profile was similar in pts with ROS1+ NSCLC with or without CNS mets. Clinical trial information: NCT03093116."

Clinical • Metastases • P1/2 data • Alzheimer's Disease • Ataxia • CNS Disorders • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • ROS1

Study to Evaluate the Effect of Repotrectinib on the Drug Levels of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

Safety and preliminary clinical activity of NVL-520, a highly selective ROS1 inhibitor, in patients with advanced ROS1 fusion-positive solid tumors (AACR-NCI-EORTC 2022) - P1/2 | "Rationally designed ROS1 tyrosine kinase inhibitors (TKIs) that surpass the limitations of FDA/EMA-approved (crizotinib/entrectinib) or other investigational agents are a medical need. The novel ROS1 TKI NVL-520 is highly selective and designed to avoid the neurologic toxicities associated with ROS1 TKIs that concurrently inhibit TRK (entrectinib/repotrectinib/taletrectinib)...Patients received a median of 3 (range: 1-9) prior anticancer therapies, including any ROS1 TKI (100%); investigational ROS1 TKI (85%, including lorlatinib in 55%, repotrectinib in 40%); ≥2 ROS1 TKIs (75%); any chemotherapy (80%); ≥2 lines of chemotherapy (50%)... NVL-520 has been well-tolerated up to 100 mg daily with favorable pharmacokinetics. Activity has been demonstrated in heavily pretreated patients (of whom 70% received ≥2 prior ROS1 TKIs plus chemotherapy), including those with brain metastases and the G2032R mutation."

Clinical • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ROS1

Effectiveness and cost-effectiveness of first-line versus second-line use of repotrectinib in the treatment of ROS1 fusion-positive advanced NSCLC. (PubMed, Expert Rev Anticancer Ther) - "Repotrectinib is not cost-effective at current prices, but first-line use is consistently more economically favorable than second-line therapy. Price reductions or shorter treatment durations could improve its cost-effectiveness."

HEOR • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Zai Lab Announces National Medical Products Administration (NMPA) Approval of AUGTYRO (repotrectinib) for Patients with NTRK-Positive Solid Tumors (Businesswire) - "The NMPA’s decision is based on the results from the pivotal Phase 1/2 TRIDENT-1 study, which demonstrated robust and durable efficacy and a manageable safety profile of repotrectinib in patients with NTRK fusion-positive solid tumors."

China approval • Solid Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), the NCCN Drugs & Biologics Compendium (NCCN Compendium), the NCCN Radiation Therapy Compendium, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Esophageal and Esophagogastric Junction Cancers, Version 1.2026. (NCCN)

NCCN guideline • Esophageal Cancer • Esophagogastric Junction Squamous Cell Carcinoma

Evolving Therapeutic Landscape of ROS1-Positive Non-Small Cell Lung Cancer: An Updated Review. (PubMed, Curr Oncol) - "Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial) (clinicaltrials.gov) - P2 | N=6 | Terminated | Sponsor: M.D. Anderson Cancer Center | N=58 ➔ 6 | Trial completion date: Dec 2027 ➔ Dec 2025 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2027 ➔ Dec 2025; <75% Participation

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), the NCCN Drugs & Biologics Compendium (NCCN Compendium), the NCCN Radiation Therapy Compendium, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Gastric Cancer, Version 1.2026. (NCCN)

dMMR • MSI-H • NCCN guideline • Gastric Cancer

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs in Japan; encorafenib for colorectal cancer, daratumumab for multiple myeloma, repotrectinib for NTRK-fusion positive solid tumors, and venetoclax for leukemia. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Colorectal Cancer • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Solid Tumor • NTRK

KRAS-Wild Pancreatic Cancer-More Targets than Treatment Possibilities? (PubMed, Cancers (Basel)) - "Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • FGFR • KRAS • NRG1 • NTRK • RET • ROS1