Apollomics Announces Initiation of SPARTA Phase 2 Clinical Trial
Apollomics, Inc. recent announced the initiation of the Phase 2 portion of the Phase 1/2 clinical trial for APL-101 based on completion of the Phase 1 and approval from the study’s safety review committee to advance the trial. APL-101 is a novel, orally administered, highly selective Type 1b class of c-MET inhibitor, an enzyme which has been shown to function abnormally in many malignant tumors.
The APL-101 Phase 1/2 clinical trial is an international multicenter, open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of APL-101. The Phase 2 portion of the study, titled SPARTA, will evaluate activity in non-small cell lung cancer (NSCLC) with a mutation that leads to MET exon 14 skipping, and across tumor types (pan-cancer) with MET amplification or fusions.
“Advancing APL-101 into our Phase 2 SPARTA trial is a major milestone for Apollomics as we strive to combat NSCLC MET exon 14 skipping and MET dysregulated tumors with precision,” said Guo-Liang Yu, PhD, Chairman and Chief Executive Officer. “The incidence of MET dysregulations presents a critical need to identify patients who can benefit most from a targeted treatment, like APL-101, in order to optimize patient care. Over the past several years, we have established numerous partnerships with leading biopharma companies, and we continue to progress our robust research and development pipeline globally.”
SPARTA will enroll patients into multiple cohorts. In NSCLC, the trial will evaluate both c-MET inhibitor naïve and experienced patients with mutations that lead to MET exon 14 skipping. Two cohorts will enroll patients with solid tumors with MET amplifications and fusions, including glioblastoma multiforme, the most aggressive form of brain cancer. The primary objective of SPARTA is to assess efficacy by overall response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) or relevant evaluation criteria per tumor type. Secondary objectives include the incidence and severity of adverse events and additional efficacy measurements, including time to progression, progression free survival, and overall survival.
“MET is dysregulated in several tumor types in addition to non-small cell lung cancer allowing for the possibility of broad applicability for a targeted treatment. Based on the tolerability data from the Phase 1 portion of SPARTA, and the emerging data observed in MET dysregulated NSCLC from a parallel ongoing Chinese Phase 1 trial, we are encouraged by the potential of APL-101. We look forward to further evaluation of APL-101 in the Phase 2 setting,” added Mark Awad, MD, PhD, SPARTA Principal Investigator, Assistant Professor of Medicine at Harvard Medical School and Clinical Director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute.
The Phase 1 portion of the study was completed in April 2020. In the study, APL-101 was generally safe and well-tolerated with no reported dose limiting toxicities, and the recommended Phase 2 dose was determined to be 200 mg twice daily (BID). Apollomics expects to present the results of the Phase 1 portion of the study at an upcoming medical meeting.
Dysregulation of the c-MET tyrosine kinase receptor is implicated in the development of tumor malignancy and can arise through several mechanisms, including gene fusion and amplification, overexpression of the receptor and/or its ligand hepatocyte growth factor (HGF), and the acquisition of activating mutations. One type of the activating mutations cause exon 14 to be skipped due to aberrant splicing of MET mRNA. MET exon 14 skipping occurs in approximately 3% of NSCLC and has been demonstrated to be an oncogenic driver, raising the possibility that tumors with these specific mutations will be largely sensitive to c-MET inhibitors.
Lung cancer is a disease in which malignant cancer cells form in the tissues of the lung. In 2017, there were an estimated 558,000 people living with lung and bronchus cancer in the United States, with new cases estimated to be over 228,000 in 2020. Lung cancer is also one of the more deadly cancers with a relative 5-year survival rate of around 20%. NSCLC is the most common type of lung cancer with about 80% to 85% of lung cancers falling into this category.
APL-101 is a novel small molecule kinase inhibitor that targets c-MET. It is a Type 1b class highly selective c-MET inhibitor. APL-101 has demonstrated strong tumor inhibitory effect in a variety of preclinical c-MET dysregulated human gastric, hepatic, pancreatic and lung cancer xenograft animal models and patient-derived xenograft models (PDX). In Phase 1 clinical trials, APL-101 (PLB1001) demonstrated a generally well-tolerated safety profile with preliminary evidence of clinical activity in NSCLC subjects harboring a mutation that leads to MET exon 14 skipping and in secondary glioblastoma multiforme (sGBM) patients harboring MET fusion and/or exon 14 skipping with evidence of brain penetration. In China, APL-101 is referred to as PLB1001 where it is being developed by Apollomics’ partner Beijing Pearl Biotechnology Co. Ltd. Details on the Phase 1/2 SPARTA clinical trial can be found on clinicaltrials.gov: NCT03175224. Apollomics is actively assessing the potential of investigating APL-101 in combination with novel therapies and in a variety of tumor types in addition to developing APL-101 as single-agent cancer therapy. APL-101 is currently under clinical investigation and not approved for any use anywhere in the world.
Apollomics, Inc., incubated by OrbiMed Asia at inception, is an innovative biopharmaceutical company committed to the discovery and development of oncology mono- and combination- therapies that harness the immune system and target specific molecular pathways to eradicate cancer. The company’s existing pipeline consists of several development-stage assets including novel, humanized monoclonal antibodies that restore the body’s immune system to recognize and kill cancer cells, and targeted therapies against uncontrolled growth signaling pathways. For more information, visit www.apollomicsinc.com.
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