ningetinib (CT053PTSA) / HEC Pharm - LARVOL DELTA

Ningetinib, a novel FLT3 inhibitor, overcomes secondary drug resistance in acute myeloid leukemia. (PubMed, Cell Commun Signal) - "Overall, our study confirmed the therapeutic role of ningetinib in AML with FLT3-ITD mutations, providing a potential new option for clinically resistant patients."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Solid Tumor • FLT3 • STAT5

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis. (PubMed, Lung Cancer) - "This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC."

Biomarker • Journal • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • EGFR

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis (Lung Cancer) - P1b | N=108 | CTR20160875 | "Between March 2017 and January 2021, 108 patients were enrolled....ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade."

Biomarker • P1 data • Non Small Cell Lung Cancer

KN046 in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=120 | Terminated | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Trial completion date: Mar 2022 ➔ Jul 2022 | Unknown status ➔ Terminated | Trial primary completion date: Mar 2021 ➔ Jul 2022; Cohort A,B,C end enrollments. Cohort D and E were considered to have no significant clinical benefit at the SMC meeting and decided to terminate enrollment.

Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preclinical characterization and phase I clinical trial of CT053PTSA targets MET, AXL, and VEGFR2 in patients with advanced solid tumors. (PubMed, Front Immunol) - "In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing."

Journal • P1 data • P1 data • Preclinical • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor • AXL • FLT3 • KDR • MERTK • MET

KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Trial completion date: Jun 2023 ➔ May 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Apr 2023 ➔ May 2022; The sponsor's development strategy adjustment resolution is terminated

Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Ningetinib (CT053PTSA) Plus Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative (clinicaltrials.gov) - P1/2 | N=158 | Active, not recruiting | Sponsor: Sunshine Lake Pharma Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2021 ➔ Jul 2023 | Trial primary completion date: Aug 2021 ➔ Jul 2023

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Not yet recruiting ➔ Active, not recruiting | N=70 ➔ 6

Enrollment change • Enrollment closed • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Ningetinib in Advanced NSCLC Skipping Mutations With MET Exon 14 Skipping Mutations (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Sunshine Lake Pharma Co., Ltd. | Trial completion date: Nov 2025 ➔ Dec 2024 | Initiation date: Aug 2021 ➔ Nov 2022 | Trial primary completion date: Nov 2025 ➔ Sep 2024

Trial completion date • Trial initiation date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] A phase Ib study of a novel c-MET, AXL and VEGFR-2 inhibitor ningetinib and gefitinib combination therapy in Chinese EGFR-TKI resistant NSCLC with T790M negative. (ASCO 2020) - P1/2 | "Ningetinib was well tolerated at 30 mg and 40 mg dosage with Gefitinib 250 mg, the RP2D for Ningetinb was 40 mg. This combination therapy showed promising anti-tumor activity in prior EGFR-TKIs acquired resistant NSCLC pts with T790M negative. C-Met GCN was the potential efficacy biomarker."

Combination therapy • P1 data • Brain Cancer • Dermatology • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • Thoracic Cancer • AXL • EGFR • FLT3 • KDR • MET

Ningetinib in Advanced NSCLC Skipping Mutations With MET Exon 14 Skipping Mutations (clinicaltrials.gov) - P2; N=80; Not yet recruiting; Sponsor: Sunshine Lake Pharma Co., Ltd.

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

A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=34; Recruiting; Sponsor: Sunshine Lake Pharma Co., Ltd.; Not yet recruiting ➔ Recruiting; Initiation date: Apr 2017 ➔ Nov 2017

Clinical • Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=12; Terminated; Sponsor: Sunshine Lake Pharma Co., Ltd.; N=34 ➔ 12; Recruiting ➔ Terminated; Company strategy adjustment

Clinical • Enrollment change • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1; N=34; Not yet recruiting; Sponsor: Sunshine Lake Pharma Co., Ltd.

Clinical • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic RCC (clinicaltrials.gov) - P1/2; N=10; Terminated; Sponsor: Sunshine Lake Pharma Co., Ltd.; N=30 ➔ 10; Recruiting ➔ Terminated; The effect of CT053PTSA in preciously treated patients with advanced and metastatic RCC is not as good as pre-expected

Clinical • Enrollment change • Trial termination • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Drug interaction of ningetinib and gefitinib involving CYP1A1 and efflux transporters in non-small cell lung cancer patients. (PubMed, Br J Clin Pharmacol) - "The high plasma exposure of M1 in patients was attributed to the inhibition of M1 efflux by ningetinib and its low tissue affinity. When co-administered, gefitinib inhibited the formation of M1, but due to the low metabolic yield of M1 in vivo, the pharmacokinetics of ningetinib was not influenced. Inhibition of CYP1A1 may increase the concentration of ningetinib in target tissues, and the long-term safety and efficacy of ningetinib combined with gefitinib should be evaluated."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP1A1

KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2; N=70; Not yet recruiting; Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Clinical • New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

First-In-Human Phase I Trial of Ningetinib ( CT053PTSA ) in the Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: Sunshine Lake Pharma Co., Ltd.

Clinical • New P1 trial • Oncology • Solid Tumor

Ningetinib (CT053PTSA) Plus Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative (clinicaltrials.gov) - P1/2; N=158; Recruiting; Sponsor: Sunshine Lake Pharma Co., Ltd.; N=72 ➔ 158; Trial completion date: Nov 2019 ➔ Nov 2021; Trial primary completion date: Aug 2019 ➔ Aug 2021

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • MET

"#CARsgen Announces Investigational #CARTTherapy #CT053 Granted PRIME Eligibility by the #EuropeanMedicinesAgency https://t.co/DukTVt2GHW" (@1stOncology)

European regulatory

Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1b; N=70; Recruiting; Sponsor: Carsgen Therapeutics, Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

CT053, Anti-BCMA CAR T-cell therapy for Relapsed/Refractory Multiple Myeloma: Proof of Concept Results from a Phase I Study (IMW 2019) - P=N/A, P1; " Patients with relapsed/refractory multiple myeloma (rrMM) who received at least 2 prior lines of therapies and between 18-79 years of age, received 1 single CT053 infusion after fludarabine/cyclophosphamide treatment. This study demonstrated that CT053 had an excellent efficacy and a good safety profile in patients with rrMM."

CAR T-Cell Therapy • P1 data

CT053, Anti-BCMA CAR T-cell therapy for Relapsed/Refractory Multiple Myeloma: Proof of Concept Results from a Phase I Study (IMW 2019) - No abstract available.

CAR T-Cell Therapy • P1 data

Umbrella study of anticancer agents in Chinese patients with NSCLC. (ASCO 2019) - "...Within biomarker matched arms, the different cohorts will test, 1) EGFR mutation for response to gefitinib, apatinib or osimertinib; 2) ALK fusion for response to crizotinib; 3) BRAF V600E mutation for response to trametinib; 4) MET amplification for response to CT053PTSA; 5) VEGFR mutation for response to apatinib or famitinib. Within the non-biomarker matched arm, cohort will test docetaxel or carboplatin... Multiple gene sequencing could be a useful selector for personalized lung cancer targeted therapy. Furthermore, mutation coexistence and mutual exclusion might be further predictors for the risk of drug resistant, recurrence at multivariate analyzes."

Clinical

Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1b; N=70; Not yet recruiting; Sponsor: Carsgen Therapeutics, Ltd.; Phase classification: P1b/2 ➔ P1b

Phase classification