Phase 2, Multicenter, Open label, Platform 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 (UNLOCK ASP3082)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Mar 2026 → ongoing

Decision date (initial)

2026-01-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astellas

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Therapy

To evaluate efficacy of ASP3082

Secondary objectives 3

1. To evaluate efficacy of ASP3082, based on investigator assessment
2. To evaluate the safety and tolerability of ASP3082
3. To better understand the mechanisms of action of ASP3082 and to describe the mechanisms of resistance to ASP3082

Conditions and MedDRA coding

Metastatic Non-small cell lung cancer (NSCLC) and Pancreatic ductal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Age ≥18 years
2. 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
3. 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
4. Patients with PDAC must have received only one prior line of chemotherapy for a minimum duration of 5 months and have experienced disease progression
5. Patients must have an ECOG performance status ≤1 at the time of screening
6. Patients must have a minimum life expectancy of 3 months
7. Patients must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria
8. 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
9. Patients must have adequate bone marrow reserve and organ function, based on local laboratory data within 21 days prior to cycle 1, day 1
10. Patients must have baseline oxygen saturation > 93% on room air
11. 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
12. 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
13. 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
14. 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
15. 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
16. Patients must be affiliated to a Social Security System or beneficiary of the same

Exclusion criteria 21

1. Patients unwilling to participate in the biological investigations and to perform blood and tissue sample collection as required in the protocol
2. Patients with NSCLC or PDAC amenable for treatment with curative intent
3. Patients with a history of severe hypersensitivity reactions to either the drug substances or any components of the formulation used
4. 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
5. Prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D
6. 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.
7. Patients with evidence of any leptomeningeal disease
8. 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
9. 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
10. 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
11. Patients have an active infection requiring intravenous antibiotic within 14 days prior cycle 1 day 1
12. Patients with clinically significant pleural effusion will be excluded and ascites requiring medical treatment within 30 days prior to ICF signature
13. 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
14. 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.
15. 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
16. Female patients who are pregnant or breastfeeding or intend to become pregnant during the study and for 6 months after study intervention administration
17. 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
18. Patients under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent
19. Patients require treatment with concomitant drugs that are strong inhibitors or inducers of CYP3A or CYP2D6
20. Participant requires treatment with concomitant drugs that are sensitive substrates of CYP2C8
21. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best overall response (BOR) based on investigator assessment per RECIST v.1.1

Secondary endpoints 3

1. Duration of response (DOR)  Clinical benefit rate (CBR)  Progression-free survival (PFS)  Overall survival (OS)
2. 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
3. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications