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임상시험 NCT07483983 (UNLOCK ASP3082)은(는) Metastatic/Locally Advanced Non-Small-Cell Lung Cancer, Metastatic/Locally Pancreatic Ductal Adenocarcinoma에 대해 모집중 상태입니다. 모든 세부 정보를 보려면 임상시험 레이더 카드 뷰와 AI 발견 도구를 확인하거나 여기에서 무엇이든 물어보세요. | ||
귀스타브 루시 연구소Study 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 (UNLOCK ASP3082) 2상 60 바이오마커 기반 오픈 라벨
Phase 2, Multicenter, Open Label, Platform Study Investigating ASP3082 in Patients With Metastaic/Locally Non-Small-Cell Lung Cancer (NSCLC) and Pancreatic Ductal Adenocarcinoma (PDAC), With Biomarker Analysis to Characterize Response/Resistance
- UNLOCK ASP3082
- 2025-522533-54-00
- 2025/4116 (기타 식별자) (CSET number (Gustave Roussy ID))
| 참가자 그룹/시험군 | 개입/치료 |
|---|---|
실험적Cohort NSCLC Patients with metastatic/locally advanced NSCLC with the presence of KRAS G12D mutation | ASP3082 Patients 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. |
실험적Cohort PDAC Patients with metastatic/locally advanced PDAC with the presence of KRAS G12D mutation | ASP3082 Patients 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. |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
Evaluate the best overall response (BOR) based on investigator assessment per RECIST v1.1 | Through treatment completion, median, 8 months |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
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. | From cycle 4 (Week 9; each cycle is 21 days) up to progression |
Clinical benefit rate (CBR) | defined as the presence of at least a PR or CR, or a stable disease (SD) \>6 months | During treatment period, response more than 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 | through treatment completion, median, 8 months |
Overall survival (OS) | Up to 18 months after EOT | |
Frequency of all adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) | Through treatment completion, median, 8 months | |
Severity of all adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) | As defined by the NCI-CTCAE v5.0 | Through treatment completion, median, 8 months |
Evaluate treatment discontinuation, interruptions, and dose reductions due to any AEs | Treatment Period, median of 8 months | |
Frequency of laboratory abnormalities | Through treatment completion, median, 8 months | |
Severity of laboratory abnormalities | Defined by NCI-CTCAE v5.0 | Through treatment completion, median, 8 months |
To understand mecanism of action of ASP3082 | This will be evaluated through the collection of tissue and blood samples throughout study | Through treatment completion, median, 8 months |
To understand the mecanism of resistance | This will be evaluated through the collection of tissue and blood samples throughout study | Through treatment completion, median, 8 months |
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
For patients with NSCLC :
- 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 with PDAC must have received only one prior line of chemotherapy for a minimum duration of 5 months and have experienced disease progression
Patients must have an ECOG performance status ≤1 at the time of screening
Patients must have a minimum life expectancy of 3 months
Patients must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria
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
Patients must have adequate bone marrow reserve and organ function, based on local laboratory data within 21 days prior to cycle 1, day 1 defined as :
- Platelet count ≥100 000/mm3 or ≥100 × 109/L (platelet transfusions are not allowed up to 14 days prior to cycle 1 Day 1 to meet eligibility)
- Hemoglobin (Hgb) ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
- Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L (use of growth factors is not allowed in the 14 days prior cycle 1)
- Creatinine clearance (CrCl) : Creatinine clearance (CrCl) ≥60 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl; confirmation of CrCl is only required when SCr is >1.5 × ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and alkaline phosphatase (ALP) <3 x ULN (or <5 x ULN for patients with liver metastases)
- Total bilirubin (TBL) <1.5 x ULN (<3 x ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinemia\]) or <2 X ULN for patients with liver metastases
- Serum albumin ≥ 3.0 g/dL
- Prothrombin time (PT) or Prothrombin time- international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT) ≤1.5 × (ULN), except for patients on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
Patients must have baseline oxygen saturation > 93% on room air
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.
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
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
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
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
Patients must be affiliated to a Social Security System or beneficiary of the same.
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.
귀스타브 루시 연구소85개의 진행 중인 임상시험 탐색 가능아스텔라스 제약90개의 진행 중인 임상시험 탐색 가능France