UNLOCK ASP3082 is an open label, single arm, multicenter, phase 2 platform study that aims to evaluate the mechanisms of action and resistance to ASP3082 in metastatic/locally advanced Non-Samll-Cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC) with the presence of KRAS G12D mutation. The two cohorts of patients are the following : i. cohort NSCLC : patients with NSCLC with KRAS G12D mutation. ii. cohort PDAC : patients with PDAC with KRAS G12D mutation. Patients enrolled in the both cohorts will receive treatment with ASP3082 at the dose of 600 mg QW thereafter in a 21-day cycle. ASP3082 will be administred in intravenous route until disease progression, unacceptable toxicity, or consent withdrawal. Tumor and blood samples will be collected at baseline, on-treatment and at the end of treatment visit only from patients who develop acquired resistance (acquired resistance is defined as a best response of CR, PR, or SD lasting more than 6 months, followed by PD).
Age ≥18 years
Patients with histologically confirmed diagnosis of locally advanced (unresectable) or metastatic NSCLC (cohort 1) or PDAC (cohort 2) and documented KRAS G12D mutation on the most recent tumor biopsy or circulating tumor DNA (ctDNA) analysis
Patients with no known targetable genomic alterations, or an alteration for which no targeted therapy is approved (or accessible), must have been treated with at least 1 line of prior therapy, including a platinum-based regimen and a PD-(L) 1 blocker, combined or sequenced, and they must have experienced progression
Patients who have known actionable genomic alterations (EGFR, BRAF, and MET mutations or ALK, ROS1, RET, NTRK fusions) must have exhausted the available targeted therapy and have experienced disease progression after a platinum-based regimen
Patients unwilling to participate in the biological investigations and to perform blood and tissue sample collection as required in the protocol
Patients with NSCLC or PDAC amenable for treatment with curative intent
Patients with a history of severe hypersensitivity reactions to either the drug substances or any components of the formulation used
Whole brain radiation therapy or stereotactic brain radiation therapy <14 days
Parallel
ASP3082
DrugPatients enrolled in both cohorts will receive treatment with ASP3082 at the dose of 600 mg QW thereafter in a 21-day cycle. ASP3082 will be administred in intravenous route until disease progression, unacceptable toxicity, or consent withdrawal.
Evaluate the best overall response (BOR) based on investigator assessment per RECIST v1.1
Duration of response (DOR)
Defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progression (PD) or death due to any cause.
Clinical benefit rate (CBR)
defined as the presence of at least a PR or CR, or a stable disease (SD) \>6 months
Progression-free survival (PFS)
Defined as the time from date of first dose until the date of the first objective documentation of disease progression or death from any cause, whichever occurs first. For patients without documented radiological progression, follow-up will be censored at the date of last radiological assessment without progression, unless death occurs within 12 weeks following the date of last known progression-free, in which case the death will be counted as a PFS event
Overall survival (OS)
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Gustave Roussy, Cancer Campus, Grand Paris
Lead sponsor
Astellas Pharma Inc
Collaborator
