Anboni (unecritinib) / Sino Biopharm - LARVOL DELTA

Safety, Efficacy, and Pharmacokinetics of Unecritinib (TQ-B3101) in Pediatric Patients with Relapsed/Refractory Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma: A Phase I Study (ASH 2024) - "Conclusion Unecritinib showed a good safety profile and promising efficacy in pediatric patients with R/R ALK+ ALCL. The RP2D of unecritinib is 300 mg BID for pediatric patients older than 10 years."

Clinical • P1 data • PK/PD data • Hematological Disorders • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • ALK • KMT2D • MET • MYCL • ROS1 • TP53

SAFETY, EFFICACY, AND GENOMIC ANALYSIS OF PEDIATRIC PATIENTS WITH RELAPSED/REFRACTORY ANAPLASTIC LYMPHOMA KINASE POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA TREATED WITH UNECRITINIB: A PHASE I STUDY (SIOP 2024) - "Background and Aims Unecritinib (TQ-B3101), which undergoes deacetylation to form crizotinib after oral administration, is a novel kinase inhibitor for ROS1, ALK and c-MET kinases, with a longer inhibition time and stronger inhibition compared to equimolar crizotinib. Except for NPM1-ALK fusion, mutation of KMT2D and TP53, amplification of MCL1 and MYC, and ESYT2-MYC fusion were also detected in seven patients, implicating their potential involvement in ALCL development and progression.Conclusions Our preliminary results suggest that unecritinib has a manageable safety profile and promising preliminary activity with durable benefits in pediatric patients with ALK+ ALCL. The RP2D of unecritinib is 300mg for patients with 10 to 18 years of age."

Clinical • Genomic analysis • Omic analysis • P1 data • Hematological Disorders • Leukopenia • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • ALK • KMT2D • MCL1 • MET • NPM1 • ROS1 • TP53

Unecritinib in Patients with ROS1 Positive Advanced Non-Small Cell Lung Cancer: Updated Results from a Phase II Trial (IASLC-WCLC 2024) - P2 | "Conclusions : In this updated analysis with longer follow-up, unecritinib continued to show the clinical benefit and manageable toxicities in ROS1-positive advanced NSCLC patients. Further analysis of OS will be performed as survival data mature."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ophthalmology • Solid Tumor • ALK • MET • ROS1

Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS：An application to pharmacokinetic studies. (PubMed, J Pharm Biomed Anal) - "The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib."

Journal • PK/PD data • Preclinical

The first domestically produced ROS1-targeting drug, another innovative drug from China Biopharmaceuticals, was approved [Google translation] (Sino Biopharm Press Release) - "On April 30, the official website of China’s National Medical Products Administration showed that the Class 1 innovative drug Unecritinib Fumarate Capsules (R&D code: TQ-B3101, trade name: Amberni) was approved for marketing by the National Medical Products Administration (NMPA), becoming the first domestic target approved for adult patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer....The company's application for marketing indication is based on a phase II single-arm, multi-center clinical study evaluating the efficacy and safety of TQ-B3101 capsule monotherapy in subjects with ROS1-positive non-small cell lung cancer."

Non-US regulatory • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial. (PubMed, Signal Transduct Target Ther) - P1, P2 | "This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC.ClinicalTrials.gov identifier: NCT03019276 and NCT03972189."

Journal • Metastases • P1/2 data • P2 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ophthalmology • Solid Tumor • ALK • MET • ROS1

Phase I Study of Tq-B3101 in Pediatric Patients with Relapsed/Refractory Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma (ASH 2022) - P1/2, P1b, P2 | "The results of ADVL0912 (NCT00939770) and A8081013 (NCT01121588) studies suggest that the ALK inhibitor crizotinib has good efficacy and safety in the treatment of ALK+ALCL. Responses were durable and ongoing, and treatment was well tolerated. Further investigation is warranted to find the MTD and confirm the efficacy of TQ-B3101."

Clinical • P1 data • Alopecia • Endocrine Disorders • Non-Hodgkin’s Lymphoma • Pediatrics • ALK • MET • ROS1

The efficacy and safety of TQ-B3101 monotherapy in the first line treatment in patients with ROS1 positive non-small cell lung cancer (ELCC 2022) - P2 | "Most common TRAEs were AST increased (73.9%), ALT increased (72.1%), emesis (63.1%), neutrophils count decrease (56.8%), leukocyte count decrease (52.3%), sinus bradycardia (52.3%), and diarrhea (43.2%). Conclusions For the first-line treatment of ROS1-positive locally advanced or metastatic NSCLC patients, TQ-B3101 showed the promising efficacy with a manageable safety profile, offering a new first-line therapeutic strategy."

Clinical • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Unecritinib Shows Efficacy as ROS1-Directed Therapy in NSCLC (Targeted Oncology) - P2 | N=111| NCT03972189 | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | "Shun Lu, MD, PhD...presented the findings at the European Lung Cancer Congress 2022....Lu noted that the occurrence of ocular organ disease was favorable, as this any-grade AE occurred in 26.1% of patients but was not found at grade 3 or higher. With results offering promising efficacy data and a manageable safety profile, unecritinib can be regarded as a new first-line treatment option."

Media quote • P2 data

Population Pharmacokinetic Modeling and Simulation of TQ-B3101 to Inform Dosing in Pediatric Patients With Solid Tumors. (PubMed, Front Pharmacol) - "The projected exposure of TQ-B3101M in virtual pediatric population following the body surface area tiered dosing regimen was similar to that in children pediatric patients after the recommended pediatric dose of crizotinib (280 mg/m2 twice daily), an analog of TQ-B3101M. A population pharmacokinetic model was developed to provide optimal dose of regimen for further development of TQ-B3101 in pediatric patients with anaplastic large cell lymphoma."

Journal • PK/PD data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Solid Tumor • ALK

A Pharmacokinetic Study of TQB3101 in Chinese Healthy Subjects (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Not yet recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Jul 2021

Clinical • Trial completion • Trial completion date

[VIRTUAL] A phase I study to evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity of TQ-B3101. (ASCO 2020) - P2 | "Preclinical studies showed TQ-B3101 had a better Inhibition activity and duration compared with equimolar crizotinib. TQ-B3101 was well tolerated and showed preliminary antitumor activity in ALK+, ROS1+ and MET amplification pts. Recommended phase II dose (RP2D) might be 300mg BID according longtime safety data. Further anti-tumor research in pts with ROS1+ is under going as multicenter clinical study in China."

Clinical • P1 data • PK/PD data • Brain Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ROS1

A Pharmacokinetic Study of TQB3101 in Chinese Healthy Subjects (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Clinical • New P1 trial

A Study of TQ-B3101 Capsules in Subjects With Advanced Malignant Tumor (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncology • Solid Tumor

A Study of TQ-B3101 Capsules in Subjects With Advanced Malignant Tumor (clinicaltrials.gov) - P2; N=200; Not yet recruiting; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Clinical • New P2 trial • Oncology • Solid Tumor

A Study of TQ-B3101 in Subjects With Relapsed or Refractory Anaplastic Large Cell Lymphoma (ALCL) (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Clinical • New P2 trial

Safety and Efficacy Study of TQ-B3101 in Patients With ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2; N=111; Recruiting; Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Newly added product (clinicaltrials.gov) - Non-Small Cell Lung Cancer, Phase 2

Pipeline update