ASP3082 for Metastatic non-small cell lung cancer | Pancreatic ductal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥18 years\n- Patients must have baseline oxygen saturation > 93% on room air\n- Females of reproductive/childbearing potential must have a negative serum or urine pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 6 months for females after the last dose of study drug. Note: Methods considered as highly effective methods of contraception include: a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation : • Oral • Intravaginal • Transdermal b. Progestogen-only hormonal contraception associated with inhibition of ovulation: • Oral • Injectable • Implantable c. Intrauterine device (IUD) d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized partner g. Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 6 months for females after the last dose of study drug. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception\n- Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 6 months after the final study drug administration\n- Male patients must be surgically sterile or must withhold heterosexual intercourse or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 3 months following the last dose of study drug\n- Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 3 months after the final study drug administration\n- Patients must understand, sign and date the written informed consent form prior to any protocol-specific procedures performed. Patients should be able and willing to comply with study visits and procedures as per protocol\n- Patients must be affiliated to a Social Security System or beneficiary of the same\n- 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\n- For patients with NSCLC: a. 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 b. 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\n- Patients with PDAC must have received only one prior line of chemotherapy for a minimum duration of 5 months and have experienced disease progression\n- Patients must have an ECOG performance status ≤1 at the time of screening\n- Patients must have a minimum life expectancy of 3 months\n- Patients must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria\n- Patients must have a tumor site easily accessible to biopsy, avoiding bone biopsy when possible. Patient must have accepted to perform pre-treatment, on-treatment, and end-of-treatment tumor and blood biopsies\n- Patients must have adequate bone marrow reserve and organ function, based on local laboratory data within 21 days prior to cycle 1, day 1"}

Exclusion criteria

• {"criterion_text":"- Patients unwilling to participate in the biological investigations and to perform blood and tissue sample collection as required in the protocol\n- 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\n- Patients have an active infection requiring intravenous antibiotic within 14 days prior cycle 1 day 1\n- Patients with clinically significant pleural effusion will be excluded and ascites requiring medical treatment within 30 days prior to ICF signature\n- Uncontrolled or significant cardiovascular disease prior to cycle 1 day 1, including: a. Corrected QT interval >470 ms for females and >450 ms for males according to Fridericia's formula (QTcF) assessed by ECG b. LVEF <50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan c. Myocardial infarction or unstable angina within 6 months d. NYHA > class II within 6 months e. Clinically significant pericardial effusion as determined by an ECHO or MUGA scan f. Symptomatic congestive heart failure, clinically significant cardiac disease\n- 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.\n- 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\n- Female patients who are pregnant or breastfeeding or intend to become pregnant during the study and for 6 months after study intervention administration\n- 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\n- Patients under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent\n- Patients require treatment with concomitant drugs that are strong inhibitors or inducers of CYP3A or CYP2D6\n- Patients with NSCLC or PDAC amenable for treatment with curative intent\n- Participant requires treatment with concomitant drugs that are sensitive substrates of CYP2C8\n- 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.\n- Patients with a history of severe hypersensitivity reactions to either the drug substances or any components of the formulation used\n- Inadequate washout period prior to cycle 1 day 1, defined as: a. Whole brain radiation therapy or stereotactic brain radiation therapy <14 days b. 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. c. 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 d. Major surgery (excluding placement of vascular access) < 28 days e. Live virus and live-attenuated vaccination <28 days f. Systemic steroid therapy or other immunosuppressive therapy < 7 days. NOTE: physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone) is permitted\n- Prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D\n- 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.\n- Patients with evidence of any leptomeningeal disease\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- Best overall response (BOR) based on investigator assessment per RECIST v.1.1","definition_or_measurement_approach":"Investigator assessment according to RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"- Duration of response (DOR)  Clinical benefit rate (CBR)  Progression-free survival (PFS)  Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Frequency and severity of all adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs), defined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)  Treatment discontinuation, interruptions, and dose reductions due to any AEs Frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0","definition_or_measurement_approach":"Adverse events and laboratory abnormalities graded/defined by NCI-CTCAE v5.0; records of treatment discontinuation, interruptions, and dose reductions"}
• {"endpoint_text":"- To evaluate pharmacodynamic changes, proteomic, genomic and other biomarkers that may correlate with treatment outcome  To characterize mechanisms of acquired resistance correlating with treatment outcome","definition_or_measurement_approach":"Assessment of pharmacodynamic, proteomic, genomic and other biomarker analyses correlated with clinical outcomes; characterization of mechanisms of acquired resistance using biomarker analyses"}

France

Earliest CTIS Part Ii Submission Date

02-01-2026

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

76

Number Of Sites

7

Number Of Participants

60

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Astellas","duties_or_roles":"Source of monetary support","organisation_type":""}