elzovantinib (TPX-0022) / ZAI Lab, BMS - LARVOL DELTA

SHIELD-1: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1 | N=95 | Active, not recruiting | Sponsor: Turning Point Therapeutics, Inc. | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

SHIELD-1: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1 | N=95 | Active, not recruiting | Sponsor: Turning Point Therapeutics, Inc. | Phase classification: P1/2 ➔ P1 | N=180 ➔ 95 | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Jan 2024

Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Structural insight into the macrocyclic inhibitor TPX-0022 of c-Met and c-Src. (PubMed, Comput Struct Biotechnol J) - "In addition, TPX-0022 exhibited potent activity against the resistance-relevant c-Met L1195F mutant and moderate activity against the c-Met G1163R, F1200I and Y1230H mutants but weak activity against the c-Met D1228N and Y1230C mutants. Overall, our study reveals the structural mechanism underlying the potency and selectivity of TPX-0022 and the ability to overcome acquire resistance mutations and provides insight into the development of selective c-Met macrocyclic inhibitors."

Journal • Oncology • Solid Tumor • CSF1R • MET

SHIELD-1: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1/2 | N=180 | Active, not recruiting | Sponsor: Turning Point Therapeutics, Inc. | Trial completion date: Nov 2023 ➔ Mar 2025 | Trial primary completion date: Nov 2023 ➔ Mar 2025

Metastases • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Activating MET Tyrosine Kinase Domain Mutations as de Novo Oncogenic Drivers in Non-small Cell Lung Cancer (IASLC-WCLC 2023) - "Importantly, two patients with lung adenocarcinoma harboring MET TKD mutations as a sole driver were enrolled into a clinical trial with a MET inhibitor called elzovantinib (TPX-0022), and experienced substantial shrinkages of the tumors. Activating MET TKD mutation was identified as the sole oncogenic mutation in a small but significant subset of NSCLC and was potentially targetable with currently available MET TKIs."

Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Activating MET Kinase Domain Mutations Define a Novel Targetable Molecular Subtype of Non-small Cell Lung Cancer that is Clinically Sensitive to MET Inhibitor Elzovantinib (TPX-0022) (IASLC-TTLC 2023) - "CONCLUSION Activating MET TKD mutations without concurrent MET exon 14 mutations were detected in ~ 0.2% of NSCLC, and occur in the absence of other known drivers in a subset of cases. Comprehensive genomic profiling to detect these alterations and guide treatment selection and clinical trial enrollment is warranted."

Clinical • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • PD-L1

SHIELD-1: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1/2 | N=180 | Active, not recruiting | Sponsor: Turning Point Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Preliminary interim data of elzovantinib (TPX-0022), a novel inhibitor of MET/SRC/CSF1R, in patients with advanced solid tumors harboring genetic alterations in MET: Update from the Phase 1 SHIELD-1 trial (AACR-NCI-EORTC 2022) - P1/2 | "Elzovantinib, a novel MET/SRC/CSF1R inhibitor, was generally well tolerated with primarily low-grade dizziness, no high-grade edema, and a favorable PK profile. The RP2D is currently under evaluation and updated safety and efficacy data will be available for presentation. A global multi-cohort Phase 2 trial of pts with MET-altered tumors is planned."

Clinical • P1 data • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CSF1R • MET

[VIRTUAL] Preliminary interim data of elzovantinib (TPX-0022), a novel inhibitor of MET/SRC/CSF1R, in patients with advanced solid tumors harboring genetic alterations in MET: Update from the Phase 1 SHIELD-1 trial (AACR-NCI-EORTC 2021) - No abstract available

Clinical • P1 data • Oncology • Solid Tumor • CSF1R

SHIELD-1: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1/2 | N=180 | Recruiting | Sponsor: Turning Point Therapeutics, Inc. | N=330 ➔ 180 | Trial primary completion date: Nov 2022 ➔ Nov 2023

Enrollment change • Metastases • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Turning Point Therapeutics and MD Anderson Announce Strategic Alliance to Advance Precision Cancer Therapies (GlobeNewswire) - "The initial focus of the alliance will be Turning Point’s lead drug candidate, repotrectinib, a next-generation kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors that is currently being studied in a registrational Phase 1/2 study (TRIDENT-1). Alliance studies also will include elzovantinib (TPX-0022), a kinase inhibitor targeting MET, CSF1R and SRC, which is currently being studied in a Phase 1 trial of patients with advanced solid tumors harboring genetic alterations in MET (SHIELD-1)....The planned focus of the alliance will include monotherapy and potential combinations with other agents – including chemotherapy, immunotherapies and other targeted agents."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MD Anderson and Turning Point Therapeutics announce strategic alliance to advance precision cancer therapies - '"There is a major unmet need to develop effective next-generation targeted therapies for cancer patients with oncogene-driven solid tumors, particularly those with mutations that render them resistant to our current therapies,' said John V. Heymach, M.D., Ph.D."

Media quote

Activating MET kinase domain mutations define a novel molecular subtype of non–small cell lung cancer that is clinically targetable with the MET inhibitor elzovantinib (TPX-0022). (ASCO 2022) - "Potentially actionable MET-TKD mutations lacking concurrent METex14 mutations represent a novel genomic subtype in 0.5-0.9% of NSCLC, and occur in the absence of other known drivers in a subset of cases."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • KRAS • ROS1

Zai Lab Announces First Quarter 2022 Financial Results and Corporate Updates (PRNewswire-Asia) - "Elzovantinib (TPX-0022) - Anticipated 2022 Zai Milestone: Enroll the first patient in Greater China in the Phase 1 expansion portion of the global Phase 1/2 SHIELD-1 study."

Trial status • Oncology • Solid Tumor

SHIELD-1: Phase 1/2 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (clinicaltrials.gov) - P1/2 | N=330 | Recruiting | Sponsor: Turning Point Therapeutics, Inc. | Phase classification: P1 ➔ P1/2 | N=120 ➔ 330

Enrollment change • Phase classification • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Turning Point Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for Combination of Elzovantinib and Aumolertinib in EGFR Mutant Met-Amplified Non-Small Cell Lung Cancer (GlobeNewswire) - "Turning Point Therapeutics...announced that the company has received clearance from the FDA for the company’s Investigational New Drug (IND) application for the combination of elzovantinib and aumolertinib in EGFR mutant MET-amplified advanced non-small cell lung cancer (NSCLC). The company expects to initiate the Phase 1b/2 SHIELD-2 combination study in mid-2022."

IND • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Turning Point Therapeutics Provides Updates and Anticipated 2022 Clinical and Discovery Pipeline Milestones (GlobeNewswire) - "The company anticipates providing a clinical data update from the Phase 1 SHIELD-1 study in the second half of 2022.; The company anticipates initiating the Phase 2 portion of the SHIELD-1 study in the second half of 2022, pending FDA feedback on data from the intermediate dose level; The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending clearance of an investigational new drug (IND) application by the FDA."

New P1/2 trial • P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Turning Point Therapeutics Provides Regulatory Updates (GlobeNewswire) - "The company participated in a Type B meeting with the FDA Division of Oncology 3 (DO3, the division responsible for oversight of gastric cancer therapeutic area). The purpose of the meeting was to discuss the proposed approach to identifying the recommended phase 2 dose (RP2D) and the planned Phase 2 portion of the SHIELD-1 study focused on the potential next steps for elzovantinib in patients with MET amplified gastric/GEJ cancer...The FDA DO3 agreed with the approach for RP2D identification previously discussed with FDA Division of Oncology 2 (DO2, the division responsible for oversight of lung cancer therapeutic area)...the company continues to enroll patients within Phase 1 dose expansion using 40 mg QD to 40 mg BID dosing and in Phase 1 dose escalation at the last anticipated dose level of 60 mg QD to 60 mg BID."

FDA event • Trial status • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zai Lab Announces Third Quarter 2021 Financial Results and Corporate Updates (GlobeNewswire) - "[For MARGENZA] Submit an NDA for pretreated metastatic HER2-positive breast cancer around year end; [for Bemarituzumab] Initiate a Phase 1b signal-seeking study of bemarituzumab alone and in combination with chemotherapy for the treatment of advanced, refractory squamous NSCLC by the first quarter of 2022. Planning is underway for signal-seeking studies in other solid tumors. [for Elzovantinib] Explore an additional intermediate dose level in at least 6-10 patients as recommended by the FDA, with the intention of revising the SHIELD-1 study into a potentially registrational Phase 1/2 study. Turning Point plans to initiate the Phase 2 portion of the SHIELD-1 study pending FDA feedback in 2022. Anticipate FDA feedback on the development path for elzovantinib in gastric/GEJ cancer in the fourth quarter of 2021. Initiate SHIELD-2, a Phase 1b/2 combination study with an epidermal growth factor receptor (EGFR) -targeted therapy in mid-2022, pending filing of an investigational..."

NDA • New P1 trial • New P1/2 trial • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics Reports Third-Quarter Financial Results, Provides Operational Updates (GlobeNewswire) - “The company anticipates discussing next steps towards registration of repotrectinib in patients with NTRK-positive TKI-pretreated advanced solid tumors at a Type B meeting with the FDA in the fourth quarter of 2021….FDA feedback on the development path for elzovantinib in gastric/gastroesophageal junction (GEJ) cancer is anticipated in the fourth quarter of 2021….Clinical collaboration with EQRx to evaluate elzovantinib in combination with aumolertinib, EQRx’s drug candidate targeting EGFR, in patients with EGFR mutant MET-amplified advanced NSCLC. The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending filing of an investigational new drug (IND) application by the FDA….The most advanced programs target KRAS G12D and the p21 activated kinase, or ‘PAK’ family. Turning Point is targeting 2 development candidates in the second half of 2022 with a goal to achieve at least one new IND per year beginning in 2023.”

FDA event • IND • New trial • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics and EQRx Announce Clinical Collaboration to Evaluate Elzovantinib in Combination with Aumolertinib in Patients with EGFR Mutant Met-Amplified Advanced Non-Small Cell Lung Cancer (GlobeNewswire) - "Turning Point Therapeutics...and EQRx...announced a clinical collaboration to evaluate elzovantinib (TPX-0022), Turning Point’s drug candidate targeting MET, SRC, and CSF1R, in combination with aumolertinib, EQRx’s drug candidate targeting EGFR, in patients with EGFR mutant MET-amplified advanced non-small cell lung cancer (NSCLC). Under the terms of the agreement, Turning Point will sponsor and conduct a Phase 1b/2 clinical trial to evaluate the safety, tolerability and preliminary efficacy of the combination regimen and will assume all costs associated with the trial. EQRx will provide aumolertinib at no cost. Turning Point is targeting initiation of the clinical trial in 2022, pending filing of an investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA)."

IND • Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics Presents Updated Preliminary Clinical Data for Repotrectinib and Elzovantinib (TPX-0022) at 2021 AACR-NCI-EORTC Conference and Provides Regulatory Updates (GlobeNewswire) - P1/2, N=450; TRIDENT-1 (NCT03093116); Sponsor:Turning Point Therapeutics, Inc; "The updated Phase 2 TRIDENT-1 dataset utilizes an August 26, 2021 data cutoff. The safety analysis includes 301 treated patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 across all cohorts, and the preliminary efficacy analysis includes 72 evaluable patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 in the ROS1-positive TKI-pretreated advanced non-small cell lung cancer (NSCLC) cohorts (EXP-2, EXP-3, EXP-4)...Across EXP-2, EXP-3 and EXP-4, 18 patients (25%) had a ROS1 resistance mutation detected, 15 of which had G2032R solvent front mutations (SFMs). The cORR was 50% (95% CI: 26-74) in 18 patients with any resistance mutation and 53% (95% CI: 27-79) in patients with a G2032R SFM which included two complete responses (CRs)."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics Presents Updated Preliminary Clinical Data for Repotrectinib and Elzovantinib (TPX-0022) at 2021 AACR-NCI-EORTC Conference and Provides Regulatory Updates (GlobeNewswire) - "Regulatory Updates: Repotrectinib - At the company’s anticipated meeting with the U.S. Food and Drug Administration (FDA) in the first half of 2022 to discuss the topline BICR results from EXP-1 of the TRIDENT-1 study, the company also plans to discuss available BICR data; Elzovantinib: At a recent End of Phase 1 Meeting with the FDA, the company received guidance on the design of the planned Phase 2 portion of the SHIELD-1 study and feedback on the recommended Phase 2 dose. The meeting focused on the potential next steps for elzovantinib in patients with NSCLC.... Based on the FDA feedback, the company plans to revise SHIELD-1 into a potentially registrational Phase 1/2 study and initiate the Phase 2 portion of SHIELD-1 in 2022 pending FDA feedback on data from the intermediate dose level. In addition, FDA feedback on the development path for elzovantinib in gastric/gastroesophageal junction (GEJ) cancer is pending."

FDA event • Trial status • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics Presents Updated Preliminary Clinical Data for Repotrectinib and Elzovantinib (TPX-0022) at 2021 AACR-NCI-EORTC Conference and Provides Regulatory Updates (GlobeNewswire) - P1, N=120; SHIELD-1 (NCT03993873); Sponsor: Turning Point Therapeutics, Inc; "A total of 46 patients were evaluable for efficacy, including 32 who were MET TKI-naïve; 11 with NSCLC, nine with GC/GEJ cancer, and 12 with other solid tumors. Of the 11 NSCLC patients, five had MET exon 14 skipping, four had MET amplification, and two had MET oncogenic mutations. Of the nine GC/GEJ cancer patients, eight had MET amplification and one had MET fusion. Of the 12 patients with advanced other solid tumors, seven had MET amplification, three had MET exon 14 skipping, and two had MET fusions...14 patients were MET TKI-pretreated; 13 with NSCLC and one with liver cancer. This population was heavily pretreated with 36% having received at least five lines of prior therapy. The median number of prior therapies was three (range 1 to 6). Seven of 13 NSCLC patients achieved stable disease as their best response for a clinical benefit rate of 54%."

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Turning Point Therapeutics Announces Additional Details for Three Data Presentations at the 2021 AACR-NCI-EORTC Conference (GlobeNewswire) - "Turning Point Therapeutics...announced additional details for its data presentations, including a late-breaking plenary presentation, from ongoing clinical trials for lead drug candidate, repotrectinib, and TPX-0022, a novel MET/SRC/CSF1R inhibitor. These data will be presented at the Virtual International Conference on Molecular Targets and Cancer Therapeutics hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) being held October 7-10."

P1 data • P2 data • Oncology • Solid Tumor