Study Investigating ASP3082 in Patients With Metastatic/Locally Advanced Non-small-cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC), With Biomarker Analysis to Characterize Response/Resistance

Exclusion Criteria33

• 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
• Inadequate washout period prior to cycle 1 day 1, defined as:
• Whole brain radiation therapy or stereotactic brain radiation therapy <14 days
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <7 days. Participant must have recovered from all radiation-related toxicities and not have active radiation pneumonitis.
• Any investigational agents or other anticancer drug(s), including immunotherapy, from a previous cancer treatment regimen or clinical study <21 days or <5 half-lives, whichever is shorter, prior to first dose of ASP3082
• Major surgery (excluding placement of vascular access) < 28 days
• Live virus and live-attenuated vaccination <28 days
• Systemic steroid therapy or other immunosuppressive therapy < 7 days.
• Prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D
• Evidence of spinal cord compression or brain metastases, defined as being clinically active (symptomatic), or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms or untreated. Patients with treated brain metastases and clinically inactive (asymptomatic) (i.e., without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Patients must have a stable neurologic status for at least 28 days prior to cycle 1 day 1.
• Patients with evidence of any leptomeningeal disease
• Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade 1 or baseline according to the NCI-CTCAE v5.0
• Any evidence of primary malignancy other than metastatic/locally advanced NSCLC or PDAC within 2 years prior to cycle 1 day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
• Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required
• Patients have an active infection requiring intravenous antibiotic within 14 days prior cycle 1 day 1
• Patients with clinically significant pleural effusion will be excluded and ascites requiring medical treatment within 30 days prior to ICF signature.
• Uncontrolled or significant cardiovascular disease prior to cycle 1 day 1, including:
• Corrected QT interval >470 ms for females and >450 ms for males according to Fridericia's formula (QTcF) assessed by ECG
• LVEF <50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• Myocardial infarction or unstable angina within 6 months
• NYHA > class II within 6 months
• Clinically significant pericardial effusion as determined by an ECHO or MUGA scan
• Symptomatic congestive heart failure, clinically significant cardiac disease
• Participant with active hepatitis B (including acute HBV or chronic HBV) or HCV (RNA detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing.
• Patient with diagnosis of human immunodeficiency virus (HIV). Patients with HIV infection on antiviral therapy and undetectable viral load are allowed with a requirement for regular monitoring for reactivation for the duration of treatment on study per local or institutional guidelines
• Female patients who are pregnant or breastfeeding or intend to become pregnant during the study and for 6 months after study intervention administration
• Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Patients under guardianship, curatorship, judicial protection, family habilitation or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent
• Patients require treatment with concomitant drugs that are strong inhibitors or inducers of CYP3A or CYP2D6
• Participant requires treatment with concomitant drugs that are sensitive substrates of CYP2C8
• Participation in another clinical trial (<30 days or <5 half-lives, whichever is longer) evaluating an experimental drug (except non-interventional research) and while on study treatment.