Anboni (unecritinib) / Sino Biopharm - LARVOL DELTA

Toxicity profiles of ROS1 tyrosine kinase inhibitors in advanced non-small cell lung cancer: a systematic review and proportional meta-analysis. (PubMed, Front Pharmacol) - "Systemic SAEs exhibited greater variability across agents, ranging from 29% to 47%: crizotinib, 43% (95% CI, 36%-49%); ceritinib, 41% (95% CI, 37%-45%); lorlatinib, 39% (95% CI, 25%-55%); entrectinib, 32% (95% CI, 28%-36%); repotrectinib, 29% (95% CI, 24%-33%); iruplinalkib, 44% (95% CI, 38%-50%); and unecritinib, 47% (95% CI, 38%-56%)...Taletrectinib and unecritinib were notably associated with hepatotoxicity...These findings will guide drug selection and safety monitoring, emphasizing the necessity of considering patients' health status, potential risk factors, and the characteristics of ROS1-TKI-related adverse reactions. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024551353, identifier CRD42024551353."

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

Efficacy and safety of TQ-B3101 as postoperative adjuvant therapy for completely resected stage IB-IIIA non-small cell lung cancer with uncommon ROS1 mutations (ChiCTR) - P2 | N=31 | Not yet recruiting | Sponsor: Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

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