zurletrectinib (ICP-723) / InnoCare - LARVOL DELTA

Title: Efficacy, safety and pharmacokinetics (PK) of zurletrectinib, a next-generation pan-TRK inhibitor, in pediatric and adolescent patients with NTRK fusion-positive (NTRK+) solid tumors (Abstract No.: 10048) (Businesswire) - "Latest data of InnoCare’s robust oncology pipelines presented at the 2025 ASCO Annual Meeting....As of Nov. 23, 2024, 18 patients in total were enrolled, including 8 pediatric patients and 10 adolescent patients. Among the 18 patients, 6 TRK inhibitor treatment-naïve patients with central lab confirmed NTRK+ were efficacy evaluable. The confirmed ORR assessed by IRC was 100%. All patients achieved partial response (PR) at the first tumor assessment and maintained the remission as of the cutoff date. Median time to response were 1.0 month in adolescent patients and 0.9 month in pediatric patients. It is worth noting that one pediatric patient who progressed on prior first-generation TRK inhibitor achieved complete response after receiving zurletrectinib."

Retrospective data • Solid Tumor

Title: Updated efficacy and safety of zurlectrectinib in adult patients (pts) with locally advanced or metastatic NTRK fusion-positive (NTRK+) solid tumors (Abstract No.: 3112) (Businesswire) - "Latest data of InnoCare’s robust oncology pipelines presented at the 2025 ASCO Annual Meeting....As of Nov. 23, 2024, a total of 49 TRK inhibitor naïve adult patients were evaluable for efficacy representing 12 different solid tumor types. Among the efficacy population, the distribution of NTRK1, NTRK2 and NTRK3 fusions was 53.1%, 2.0% and 44.9% respectively. The confirmed ORR by IRC was 83.7%, with CR of 10.2%. Median duration of response (DOR) and median progression-free survival (PFS) by IRC were not reached. The DOR rate and PFS rate by IRC at 12 months was 92.0% and 90.5% respectively. Two of the three patients who had brain metastasis at the baseline achieved intracerebral ORR, which is consistent with the good brain penetration and strong intracranial activity of zurletrectinib."

Retrospective data • Solid Tumor

Efficacy, safety and pharmacokinetics (PK) of zurletrectinib, a next-generation pan-TRK inhibitor, in pediatric and adolescent patients (pts) with NTRK fusion-positive (NTRK+) solid tumors. (ASCO 2025) - P1/2 | "The integrated analysis demonstrated that zurletrectinib had significant efficacy and good safety profile in pediatric and adolescent pts with NTRK+ solid tumors. Zurletrectinib also showed the potential to overcome the resistance to 1st generation TRK inhibitors. These findings support zurletrectinib is a better treatment option for NTRK+ pediatric and adolescent pts."

Clinical • PK/PD data • Anemia • Fibrosarcoma • Hematological Disorders • Oncology • Pediatrics • Sarcoma • Solid Tumor • NTRK

Updated efficacy and safety of zurlectrectinib in adult patients (pts) with locally advanced or metastatic NTRK fusion–positive (NTRK+) solid tumors. (ASCO 2025) - P1/2 | "In line with previously reported results, zurlectrectinib continued to demonstrate a deep and durable responses in adult pts with NTRK+ advanced solid tumors with or without brain metastasis. Zurlectrectinib was also well-tolerated and showed favorable safety profile in adult pts with various tumor types."

Clinical • Metastases • Anemia • Hematological Disorders • Oncology • Solid Tumor • NTRK • NTRK1 • NTRK2 • NTRK3

InnoCare’s Zurletrectinib Receives Priority Review from China’s NMPA (Businesswire) - "InnoCare Pharma...announced today that its new generation pan-TRK inhibitor zurletrectinib (ICP-723) has been granted priority review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA), which accepted the New Drug Application (NDA) of zurletrectinib for the treatment of patients with advanced solid tumors harboring NTRK gene fusions recently....In the registrational trial for patients with NTRK fusion-positive solid tumors, zurletrectinib demonstrated outstanding efficacy with a good safety profile."

China filing • Evidence highlight • Priority review • Solid Tumor • NTRK

InnoCare Announces the Acceptance of New Drug Application for pan-TRK Inhibitor Zurletrectinib in China (Businesswire) - "InnoCare Pharma...announced today that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) accepted a New Drug Application (NDA) for its new generation pan-TRK inhibitor zurletrectinib (ICP-723) for the treatment of adult and adolescent patients (12 to 18 years old) with advanced solid tumors harboring NTRK gene fusions. In the registrational trial for adult and adolescent patients with NTRK fusion-positive solid tumors, zurletrectinib demonstrated outstanding efficacy with a good safety profile. Zurletrectinib was also shown to overcome acquired resistance to the first-generation TRK inhibitors. Meanwhile, the Company is accelerating the registrational trial for pediatric patients (2 to 12 years old)."

China filing • Trial status • Solid Tumor

Study of ICP-723 in Patients with Advanced Solid Tumors or Primary Central Nervous System Tumors (clinicaltrials.gov) - P1/2 | N=55 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Jun 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Oncology • Solid Tumor • NTRK

InnoCare Releases 2024 Interim Results and Business Highlights (Businesswire) - N=P1/2 | N=310 | NCT04685226 | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | "Zurletrectinib has demonstrated good efficacy and safety profile....The clinical study with zurletrectinib has covered neurotrophic tyrosine receptor kinase (NTRK) gene fusion adult patients, adolescent patients (12 to 18 years old) and pediatric patients (2 to 12 years old). The efficacy has been observed in both adolescent and pediatric patients. The dose escalation trial for pediatric patients has been completed."

P1/2 data • Oncology • Solid Tumor

British Journal of Cancer: Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation agents (Businesswire) - "InnoCare announced British Journal of Cancer...recently published a paper entitled 'Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation agents'. The journal concluded that zurletrectinib is a novel, highly potent next-generation TRK inhibitor with higher in vivo brain penetration and stronger intracranial activity than other next-generation agents....Zurletrectinib (1 mg/kg BID) inhibited tumor growth in xenograft models derived from NTRK fusion-positive cells at a dose 30 times lower when compared to selitrectinib....In an orthotopic mouse glioma xenograft model carrying the TRKA G598R/G670A resistance mutation, zurletrectinib (15 mg/kg) significantly improved the survival of mice harboring orthotopic NTRK fusion-positive, TRK-mutant gliomas (median survival = 41.5, 66.5, and 104 days for selitrectinib, repotrectinib, and zurletrectinib respectively..."

Preclinical • Glioma

Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents. (PubMed, Br J Cancer) - "Our data identifies zurletrectinib as a novel, highly potent next-generation TRK inhibitor with stronger in vivo brain penetration and intracranial activity than other next-generation agents."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • NTRK • NTRK2 • NTRK3

InnoCare Releases 2023 Results and Business Highlights (Businesswire) - "Zurletrectinib (ICP-723): InnoCare is accelerating the registrational trial of zurletrectinib in China. The NDA is expected to be submitted by the end of 2024....The Company is conducting a clinical trial of zurletrectinib for pediatric (2 to 12 years old) and adolescent patients (12 to 18 years old). Patient enrollment of pediatric patients is ongoing, with PR observed."

Non-US regulatory • Trial status • Oncology • Solid Tumor

A Phase I/II Clinical Trial of ICP-723 in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=310 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | N=42 ➔ 310

Enrollment change • Oncology • Solid Tumor

InnoCare Announces First Pediatric Patient Dosed in Clinical Trial of pan-TRK Inhibitor Zurletrectinib in China (Businesswire) - "InnoCare Pharma...announced today that the first pediatric patient has been dosed in clinical trial with its second generation pan-TRK inhibitor zurletrectinib at Sun Yat-sen University Cancer Center. This is the first time that zurletrectinib will be evaluated in a clinical study of pediatric (2 to 12 years old) patients, after demonstrating good safety and efficacy in adult and adolescent patients (12 to 18 years old)."

Trial status • Solid Tumor

Zurletrectinib, a next-generation TRK inhibitor shows strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation drugs. (AACR-NCI-EORTC 2023) - No abstract available

Oncology • NTRK

InnoCare Releases 2023 Interim Results and Business Highlights (Businesswire) - "Patient enrollment of the registrational trial of tafasitamab in combination with lenalidomide for the treatment of r/r DLBCL was completed in China. The Company expects to submit the biologics license application (BLA) in the second quarter of 2024 and anticipate BLA approval in the first half of 2025; ICP-248...The Company expects to submit an investigational new drug (IND) application in the U.S. within this year....InnoCare is accelerating the registrational trial of zurletrectinib in China and expecting to submit NDA by end of 2024."

BLA • Enrollment closed • IND • NDA • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

InnoCare Announces Approval of Clinical Trial of pan-TRK Inhibitor Zurletrectinib for the Treatment of Pediatric Patients in China (Businesswire) - "InnoCare Pharma...announced today that the Company has received approval to conduct clinical trial of its second generation pan-TRK inhibitor zurletrectinib (ICP-723) to treat pediatric patients (2 to 12 years old) in China. This is following the clinical trial of zurletrectinib for adolescent patients (12 to 18 years old) after showing good safety and efficacy in adult patients. Zurletrectinib was developed to treat advanced or metastatic solid tumors harboring NTRK fusion genes, including breast cancer, colorectal cancer, lung cancer, thyroid cancer, sarcoma, etc., and for patients resistant to the first generation of TRK inhibitors."

New trial • Breast Cancer • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Sarcoma • Solid Tumor • Thoracic Cancer • Thyroid Gland Carcinoma

A Phase 2 Study of ICP-723 in Patients With Advanced Solid Tumors or Primary Central Nervous System Tumors (clinicaltrials.gov) - P1/2 | N=55 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Metastases • New P1/2 trial • Brain Cancer • CNS Tumor • Oncology • Solid Tumor • NTRK

Evaluate the Safety, Tolerability, and Pharmacokinetics of ICP-723 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: InnoCare Pharma Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Safety, pharmacokinetics (PK), and clinical efficacy of ICP-723, a highly selective next-generation pan-TRK inhibitor, in patients with solid tumor. (ASCO 2022) - P1/2 | "ICP-723 is safe and well-tolerated in patients with advanced solid tumors. Encouraging clinical efficacy including intracranial activity was demonstrated in patients with NTRK gene fusion in various tumor types. Enrollment in phase I is ongoing until the final RP2D is determined, then phase II expansion will be conducted in patients with defined gene alterations."

Clinical • PK/PD data • Anemia • Hematological Disorders • Immunology • Oncology • Pain • Pediatrics • Solid Tumor • NTRK • NTRK1 • NTRK2 • NTRK3

InnoCare Announces First Adolescent Patient Dosed in Clinical Trial of pan-TRK Inhibitor ICP-723 in China (Businesswire) - "InnoCare Pharma...announced today that the first adolescent patient has been dosed in clinical trial with its second generation pan-TRK inhibitor ICP-723 at the Sun Yat-sen University Cancer Center. This is also the first time that ICP-723 will be evaluated in the clinical study of adolescent (12 to 18 years old) patients after showing good safety and efficacy in adult patients....Based on the Proof-of-Concept (POC) data obtained, InnoCare will promote a registration clinical study of ICP-723 in China. The Company has also conducted a clinical study of ICP-723 in the United States. Currently there was no dose-limiting toxicities (DLTs) observed at the first dose group."

Trial status • Oncology • Solid Tumor

Evaluate the Safety, Tolerability, and Pharmacokinetics of ICP-723 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: InnoCare Pharma Inc.

New P1 trial • Oncology • Solid Tumor

Latest Data of InnoCare’s Robust Oncology Pipelines Presented at the 2022 ASCO Annual Meeting (Businesswire) - P1/2 | N=45 | NCT04685226 | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | "Latest data of InnoCare’s robust oncology pipeline were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting....As of 11 Feb 2022, a total of 17 patients in phase I dose escalation were treated with ICP-723 at doses of 1 mg QD, 2mg QD, 3mg QD, 4mg QD, 6mg QD and 8 mg QD.... According to RECIST 1.1 criteria, among the 6 patients with NTRK fusion, the overall response rate (ORR) was 66.7% (4 patients with partial response (PR)), the disease control rate (DCR) was 100%. The ORR was 100% in dose groups of 4mg and above."

P1 data • Oncology • Solid Tumor

ICP-723 is a potent pan-TRK Inhibitor with robust anti-tumor activities against wild-type and acquired drug-resistant mutations of NTRK fusions (AACR 2022) - "Clinical application of 1st generation TRK inhibitors, i.e., larotrectinib and entrectinib, for the treatment of NTRK fusion-positive cancer patients has achieved high response rates regardless of tumor types...Treatment with 1 mg/kg of ICP-723 results in 89.5% TGI of KM12 tumors, similar to the efficacies of larotrectinib or selitrectinib at 30 mg/kg dose levels... ICP-723 is a novel, 2nd generation pan-TRK inhibitor with broad-spectrum anti-tumor activities against wild-type and various acquired drug-resistant mutations of NTRK gene fusions. ICP-723 is now in phase I clinical trial in China and United States."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ETV6 • LMNA • NTRK • NTRK1 • NTRK2 • NTRK3 • TPM3

InnoCare Presents Pre-Clinical Data of ICP-723 at AACR Annual Meeting 2022 (Businesswire) - "The study showed that ICP-723 effectively inhibits kinase activities of TRKA, TRKB, TRKC with IC50 values < 1 nM....ICP-723 demonstrates robust in vitro efficacy in all wild-type TRK-driven tumors. It also overcomes solvent front mutations (e.g., TRKA G595R, TRKC G623R/E) often developed following first generation TRK inhibitor treatment....In vivo efficacy studies further demonstrate its robust anti-tumor efficacies in xenograft models. Treatment with 1 mg/kg of ICP-723 results in 89.5% TGI of KM12 tumors....The pharmacokinetic parameters of ICP-723 are overall favorable, with high oral bioavailability....'InnoCare is now conducting clinical trial of ICP-723 in China and U.S., and please stay tuned on the latest clinical data in the upcoming international conference'"

Clinical data • Preclinical • Oncology

InnoCare Announces Clearance by U.S. FDA of Clinical Trial of pan-TRK Inhibitor ICP-723 (PRNewswire) - "InnoCare Pharma...announced today the Investigational New Drug (IND) clearance of its second-generation pan-TRK inhibitor ICP-723 by the US Food and Drug Administration (FDA) for starting phase I clinical trial in the United States...The clinical trial will evaluate the safety, tolerability and pharmacokinetic properties of ICP-723 in patients with solid tumors, and evaluate the anti-tumor efficacy of ICP-723 on NTRK fusion-positive cancers."

IND • Oncology • Solid Tumor