andamertinib (PLB1004) / Avistone Biotech - LARVOL DELTA

Vebreltinib plus PLB1004 in EGFR-mutated NSCLC with acquired MET amplification or overexpression after failure on EGFR-TKI treatment: A phase Ib/II study. (ASCO 2025) - P1/2 | "Vebreltinib and PLB1004 at RP2D demonstrates notable efficacy and manageable safety in EGFR-mutated NSCLC with METamp or METov after EGFR-TKIs failure. Findings from our phase Ib+II data suggest that NGS reported METamp+ could be utilized to identify target patients to receive combination of PLB1004 + Vebreltinib. Further studies are warranted to confirm these findings."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Avistone Announces Encouraging Results for Vebreltinib plus Andamertinib (PLB1004) in EGFR-mutated NSCLC with MET Amplification or Overexpression at ASCO Annual Meeting 2025 (Businesswire) - P1b/2 | N=156 | KYLIN-1 (NCT06343064) | Sponsor: Avistone Biotechnology Co., Ltd. | "The results from Phase Ib/II KYLIN-1 study (NCT06343064) showed that Vebreltinib plus Andamertinib demonstrated notable efficacy and manageable safety in EGFR-mutated NSCLC patients with MET amplification or overexpression after EGFR-TKIs failure. Among the 56 patients enrolled at a dose of Vebreltinib 150mg BID plus Andamertinib 80mg QD (RP2D), the confirmed overall response rate (ORR) was 50.0%, and the median progression-free survival (mPFS) was 9.9 months. In 19 patients with brain metastases, ORR was 42.1% and mPFS was 9.5 months. Grade 3 or higher treatment related adverse events (TRAEs) occurred in 19.6% of the patients. None discontinued treatment or died due to TRAEs. No new safety signal was observed."

P1/2 data • Non Small Cell Lung Cancer

Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI (clinicaltrials.gov) - P1/2 | N=156 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

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

Vebreltinib Plus PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFRm, MET+, Locally Advanced or Metastatic NSCLC Following EGFR-TKI Failure (clinicaltrials.gov) - P3 | N=278 | Not yet recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Kannon: A Phase Ⅱ Study Assessing the Safety and Efficacy of PLB1004 in EGFR ex20ins Mutation Patients With Advanced and Metastatic Non-small Cell Lung Cancer(NSCLC) (clinicaltrials.gov) - P2 | N=157 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Trial completion date: Sep 2026 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Mar 2025

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

Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans. (PubMed, Cancer Chemother Pharmacol) - "Fecal excretion emerged as PLB1004 excretion route, while urinary excretion via the kidneys served as the secondary route. The primarily metabolic pathways are oxidation, demethylation, dehydrogenation, and cysteine conjugation in humans."

Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Kannon: A Phase Ⅱ Study Assessing the Safety and Efficacy of PLB1004 in EGFR Ex20ins Mutation Patients with Advanced and Metastatic Non-small Cell Lung Cancer(NSCLC) (clinicaltrials.gov) - P2 | N=157 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Trial primary completion date: Apr 2024 ➔ Oct 2024

EGFR exon 20 • Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Vebreltinib Plus PLB1004 In EGFR-Mutated, NSCLC with MET Amplification or MET Overexpression Following EGFR-TKI (IASLC-WCLC 2024) - P1/2 | "No patients discontinued treatment due to TRAEs. Conclusions : Vebreltinib plus PLB1004 showed promising antitumor activity and a manageable safety profile in patients with EGFRm NSCLC with MET amplification or MET overexpression who have experienced disease progression after prior EGFR-TKI therapy, especially in those bearing brain metastases and treated with third-generation EGFR-TKI."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Avistone Announces Results from a Sponsored Clinical Research Program Studying the Combination of Two Small-Molecule c-MET and EGFR Inhibitors in NSCLC Patients at the 2024 World Conference on Lung Cancer (WCLC) (Businesswire) - P1b/2 | N=156 | NCT06343064 | Sponsor: Avistone Biotechnology Co., Ltd. | "Forty-four patients received Vebreltinib 100mg plus PLB1004 160mg (n=15), Vebreltinib 150mg plus PLB1004 160mg (n=13), Vebreltinib 200mg plus PLB1004 80mg (n=3), or Vebreltinib 150mg plus PLB1004 80mg (n=13) and were included in the overall safety analysis. Among the 44 patients evaluated, 36.4% of patients had brain metastases and 86.4% of patients had previously received a third-generation EGFR-TKI, respectively. Objective responses occurred across all Vebreltinib and PLB1004 dose levels tested, with partial responses (PRs) observed in 19/32 (59.4%) response-evaluable patients. Among patients with brain metastases, the ORR was 75.0% (9/12). The ORR was 58.6% (17/29) in patients who received prior third-generation EGFR-TKI."

P1/2 data • Non Small Cell Lung Cancer

Vebreltinib Plus PLB1004 as the First-line Therapy for Patients With EGFRm+/MET+ Locally Advanced or Metastatic NSCLC. (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

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

A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=81 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Active, not recruiting ➔ Recruiting | Initiation date: Nov 2023 ➔ Jul 2024

Enrollment open • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI (clinicaltrials.gov) - P1/2 | N=156 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

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

Efficacy and Safety Evaluation of PLB1004 in Patients With Non-squamous NSCLC Harboring EGFR Exon 20 Insertion. (clinicaltrials.gov) - P3 | N=327 | Not yet recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=82 | Active, not recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=82 | Not yet recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Kannon: A Phase Ⅱ Study Assessing the Safety and Efficacy of PLB1004 in EGFR ex20ins Mutation Patients With Advanced and Metastatic Non-small Cell Lung Cancer(NSCLC) (clinicaltrials.gov) - P2 | N=157 | Recruiting | Sponsor: Avistone Biotechnology Co., Ltd.

EGFR exon 20 • Metastases • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Assessing the Safety and Efficacy of PLB1004 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1 | N=91 | Active, not recruiting | Sponsor: Avistone Biotechnology Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2023 ➔ Nov 2024 | Trial primary completion date: May 2022 ➔ Apr 2023

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Avistone to initiate Phase I NSCLC trial in the US (Clinical Trials Arena) - "Beijing, China-based Avistone Biotechnology is planning to initiate a Phase I trial investigating PLB-1004 in patients with non-small cell lung cancer (NSCLC) in the US. The study is expected to start in H2 2023..."

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

Interim results of a first-in-human, dose escalation and expansion study of PLB-1004, an irreversible inhibitor of exon 20 insertion mutations in patients with non-small cell lung cancer (AACR 2023) - "In the ongoing Phase 1 study, PLB1004 appears to be safe and well-tolerated with promising anti-tumor activity in patients with NSCLC harboring EGFR exon 20 insertion mutations."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Avistone Announces Interim Data Results on PLB1004 in Patients with EGFR mutant NSCLC Patients at AACR 2023 (Businesswire) - P1 | N=91 | NCT05347628 | Sponsor: Avistone Biotechnology Co., Ltd. | "At the cutoff date for these interim results, July 31, 2022, a total of 65 patients (32 in escalation and 33 in expansion) had received treatment with PLB1004. Dose escalation ranged from a starting dose of 10 mg QD to a top dose of 480 mg QD in 11 cohorts of patients. As of July 31, 2022, dose expansion occurred at two dose levels, 320 mg QD and 400 mg QD....Across all dose groups, a total of 38 subjects had EGFR Ex20ins mutations, including 29 at doses ≥ 160 mg QD, among whom 26 completed at least 1 tumor assessment. In these 26 patients the confirmed best response rate was 57.7% (15/26) and the disease control rate (DCR) was 100% (26/26)."

EGFR exon 20 • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR