varlitinib (ASLAN001) / ASLAN Pharma, Pfizer, Blade Entertaintment - LARVOL DELTA

Phase II Study to Assess the Efficacy of ASLAN001 Plus Capecitabine in CNS Metastases for HER2+ Breast Cancer (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: National Cancer Centre, Singapore

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

The Ideal Second-Line Treatment Options for Patients with Advanced Biliary Tract Cancer Refractory to Gemcitabine-Based First-Line Chemotherapy: A Result From Bayesian Network-Meta Analysis. (PubMed, Asian Pac J Cancer Prev) - "The combination of oral capecitabine with varlitinib could be a promising second-line treatment for patients with advanced biliary tract cancer refractory to gemcitabine-based first-line regimen."

Journal • Retrospective data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Tumor spatial transcriptomics and potential mechanisms of intrinsic resistance to HER2-directed therapy. (ASCO 2025) - " We conducted a phase II trial of NAC with dual HER2 blockade (12 weeks trastuzumab + HER2 tyrosine kinase inhibitor varlitinib + paclitaxel), followed by surgery, in stage I-III HER2+ BC pts. Spatial transcriptomics analyses reveal tumor and immune microenvironment heterogeneity between pCR and non-pCR pts to neoadjuvant HER2-targeted therapy. This heterogeneity may explain intrinsic resistance and could unravel potential therapeutic targets in resistant HER2+ breast cancer."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • TNFA

Varlitinib and Paclitaxel for EGFR/HER2 Co-Expressing Advanced Gastric Cancer: a Multicenter Phase Ib/II Study (K-MASTER-13). (PubMed, Cancer Res Treat) - "No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy."

Journal • Metastases • P1/2 data • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • EGFR • ERBB4 • HER-2

Two-Part, Phase Ib/II, Open Label, Single-Arm, Multi-center Study to Evaluate the Safety and Efficacy of Varlitinib in Combination With Weekly Paclitaxel in EGFR/HER2 Co-expressing Advanced or Metastatic Gastric Cancer Patients (clinicaltrials.gov) - P1/2 | N=27 | Completed | Sponsor: Yonsei University | Active, not recruiting ➔ Completed | N=62 ➔ 27

Combination therapy • Enrollment change • Metastases • Trial completion • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Analysis of ctDNA in EGFR/HER2 co-expressing advanced gastric cancer treated with second-line varlitinib and paclitaxel chemotherapy (K-MASTER-13) (KSMO 2023) - No abstract available

Circulating tumor DNA • Clinical • Metastases • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Differential Protein Expression in Response to Varlitinib Treatment in Oral Cancer Cell Line: an In Vitro Therapeutic Approach. (PubMed, Appl Biochem Biotechnol) - "Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and β-Actin as complementary/prognostic markers of OSCC."

Journal • Preclinical • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HSPA5 • VIM

Multicenter phase 2 trial of varlitinib versus lapatinib in combination with capecitabine in patients with HER2+ metastatic breast cancer (MBC) who failed prior trastuzumab therapy (ESMO Asia 2017) - P2a/2b; "Sensitivity analysis showed greater tumor size reduction and improved ORR for VC arm when the combination was administrated for more than 30 days. Reduced intended exposure and dose intensity for the VC arm suggests a dose reduction of varlitinib may be considered when combined with capecitabine for the 2nd line treatment of HER2+ MBC."

Clinical • Combination therapy • P2 data • HER2 Breast Cancer

Efficacy and safety of varlitinib, a reversible pan-HER tyrosine kinase inhibitor, in combination with platinum-based regimens in biliary tract cancers: A pooled analysis from three phase I studies. (ASCO-GI 2019) - P1, P1b/2; " Data from BTC pts were pooled from 3 Ph1 trials of varlitinib (dosed 200-500 mg BID) in combination with cisplatin and 5-FU/capecitabine (cape) (Study 002); oxaliplatin and 5-FU/cape (Study 002SG); cisplatin and gemcitabine (Study 007). Varlitinib with platinum-based chemotherapy has a promising efficacy and safety profile in BTC. A Ph2/3 randomised study of varlitinib and cape in 2nd line BTC and a Ph1b/2 study of varlitinib with platinum-based chemotherapy in 1st line BTC are ongoing."

Combination therapy • P1 data • Retrospective data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Urothelial Cancer

A multicenter, phase Ib/2 study of varlitinib plus gemcitabine and cisplatin (gem/cis) for treatment of naïve, advanced, or metastatic biliary tract cancer (BTC). (ASCO-GI 2019) - P1b/2; "Varlitinib plus gem/cis was well tolerated in the 200 mg cohort; the 300 mg cohort is ongoing. Preliminary anti-tumour activity was observed. Data will be updated at the time of presentation."

Clinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology

[VIRTUAL] Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action? (ASCO 2020) - P2a/2b | "Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity."

Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Dose finding study of varlitinib trastuzumab with carboplatin/paclitaxel in advanced solid tumors. (ASCO 2018) - P2; "The RD of V combined with P is 300mg BD int, and is active in HER2+ MBC; T can be added safely. The triple combination will be evaluated as neoadjuvant therapy in HER2+ breast cancer."

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective. (PubMed, Front Immunol) - "ICs of FDA-approved chemotherapeutic drugs capable of inhibiting DNA synthesis, including teniposide, dacarbazine, and doxorubicin, as well as inhibitors of hypoxia-inducible factor, MCL-1, ribonucleotide reductase, and FASN in clinical trials were negatively correlated with YAP1 expression. The tumor-promoting activity of YAP1 is attributed to the activation of TGF-β, Hedgehog, and KRAS signaling pathways. AZD2858 and varlitinib might be effective in cancer patients with high YAP1 expression."

Journal • Pan tumor • Immune Modulation • Immunology • Inflammation • Oncology • CAFs • CD4 • CD8 • FASN • KRAS • MCL1 • MSI • TGFB1 • TMB • YAP1

Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A. (PubMed, Front Immunol) - "However, in 6-month-old tau-overexpressing PS19 mice, varlitinib only significantly diminished astroglial activation and tau phosphorylation at Thr212/Ser214. Taken together, our findings suggest that varlitinib has therapeutic potential for LPS- and tau-induced neuroinflammatory responses and the early stages of tau pathology."

Journal • Inflammation • Oncology • EGFR • IL1B • NLRP3

Varlitinib in combination with gemcitabine and cisplatin for treatment-naïve advanced biliary tract cancer. (ASCO-GI 2022) - P1b/2 | "Varlitinib combined with gemcitabine plus cisplatin was well tolerated and associated with preliminary anti-tumor activity in patients with treatment-naïve advanced BTC."

Combination therapy • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Initial signals of efficacy in cholangiocarcinoma from a phase Ib trial of varlitinib in combination with doublet chemotherapy (cisplatin + 5-fluororacil or capecitabine). (ASCO 2017) - P1; "The combination of varlitinib and CIS + 5-FU or CAP doublet chemotherapy is safe, well tolerated and has demonstrated strong efficacy signals in cholangiocarcinoma."

Clinical • Combination therapy • P1 data • Biliary Cancer • Biosimilar • Colorectal Cancer • Gastric Cancer • Hepatocellular Cancer • HER2 Breast Cancer • Immunology • Pain • Renal Disease

Multicenter phase Ib/II study of second-line varlitinib and paclitaxel in patients with EGFR/HER2 co-expressing advanced gastric cancer (K-MASTER-13) (ESMO 2022) - "Conclusions Varlitinib combined with paclitaxel revealed manageable toxicities and antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy. Updated outcomes for ongoing patients and biomarker analysis will be presented."

Clinical • P1/2 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • ERBB4 • HER-2

Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response? (PubMed, Cancer Med) - P2a/2b | "The therapeutic responses differed across tumors' locations; the magnitude of the differences of responses across the tumors' locations were drug-dependent. Stratified analysis of the response by tumor location improved drug comparisons and is a powerful tool to understand TL heterogeneity."

Journal • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Two-Part, Phase Ib/II, Open Label, Single-Arm, Multi-center Study to Evaluate the Safety and Efficacy of Varlitinib in Combination With Weekly Paclitaxel in EGFR/HER2 Co-expressing Advanced or Metastatic Gastric Cancer Patients (clinicaltrials.gov) - P1/2 | N=62 | Active, not recruiting | Sponsor: Yonsei University

Combination therapy • New P1/2 trial • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. (PubMed, Target Oncol) - P2 | "The recommended phase II dose of varlitinib with paclitaxel is 300 mg twice daily intermittently dosed. This is active in HER2+ metastatic breast cancer. Subcutaneous trastuzumab can be added safely to varlitinib and paclitaxel. This combination is currently being evaluated as neoadjuvant therapy in HER2+ breast cancer (NCT02396108)."

Journal • P1 data • Breast Cancer • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • Neutropenia • Oncology • Solid Tumor • EGFR • ERBB4 • HER-2

Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line) (clinicaltrials.gov) - P2/3 | N=52 | Completed | Sponsor: Aslan Pharmaceuticals | Active, not recruiting ➔ Completed | N=400 ➔ 52

Combination therapy • Enrollment change • Trial completion • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp). (PubMed, ESMO Open) - "In patients with advanced biliary tract cancer, second-line treatment with varlitinib plus capecitabine was well tolerated but did not improve efficacy versus capecitabine alone. A PFS benefit was suggested in female patients and those with gallbladder cancer."

Clinical • Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • HER-2

Efficacy and safety of varlitinib, a reversible pan-HER tyrosine kinase inhibitor, in combination with platinum-based regimens in biliary tract cancers: A pooled analysis from three phase I studies. (ASCO-GI 2019) - P1, P1b/2; " Data from BTC pts were pooled from 3 Ph1 trials of varlitinib (dosed 200-500 mg BID) in combination with cisplatin and 5-FU/capecitabine (cape) (Study 002); oxaliplatin and 5-FU/cape (Study 002SG); cisplatin and gemcitabine (Study 007). Varlitinib with platinum-based chemotherapy has a promising efficacy and safety profile in BTC. A Ph2/3 randomised study of varlitinib and cape in 2nd line BTC and a Ph1b/2 study of varlitinib with platinum-based chemotherapy in 1st line BTC are ongoing."

Combination therapy • P1 data • Retrospective data

The challenge of evaluating new targeted therapies: Opportunities in stratifying the therapeutic response per tumour location (ESMO Asia 2019) - P2a/2b; "We propose to compare the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) in analyzing the changes of tumor’s volume per tumor’s locations in patients with HER2-positive metastatic breast cancer after trastuzumab therapy. The therapeutic response differed across tumor locations, the differential response was drug-dependent. For a fair comparison, the proportion of tumor at each tumor location must be balanced between arms. The stratification of the therapeutic response can be used for assessing new therapies, helping designing cocktails or refining drug’s indications.Legal entity responsible for the study: Median Technologies/Aslan Pharmaceuticals."

Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • HER-2

Phase I study: Safety and tolerability of Varlitinib (VAR) in combination with Oxaliplatin and Capecitabine (COX) or Oxaliplatin and 5-FU (FOL) in advanced solid tumours (ESMO 2018) - P1; "...COX (Capecitabine 850mg/m2 BID D1-D14 with oxaliplatin (OX) 130mg/m2 IV D1, Q21 days) or mFolfox6 (5-FU 400mg/m2 IV bolus D1 and 2400mg/m2 over 46 hrs with OX 85mg/m2 IV D1, Leucovorin 400mg/m2 IV D1, Q14 days) was given with VAR 200-400mg BID...5 (18%) had long PFS (223-645 days), comprising a gallbladder and CRC (both HER2-overexpressing, prior platinum), CC, bladder and CRC (prior OX and cetuximab)... MTD for VAR with COX and FOL was 300mg/BID. Durable efficacy was seen in biliary cancers and CRC. ASLAN pharmaceuticals and the Singapore National Medical Research Council supported this study."

Clinical • Combination therapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Urothelial Cancer