Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 2
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
mars 2026
octobre 2027
02 avril 2026
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).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Yohann LORIOT | 17/04/2026 11:05:05 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges François Leclerc - Dijon - France | François GHIRINGHELLI | Contact (sur clinicalTrials) | |||
| Gustave Roussy - 94800 - Villejuif - France - France | Yohann Loriot, MD, PhD | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Bordeaux - France | Véronique DEBIEN | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de Lorraine - Vandœuvre-lès-Nancy - France | Aurélien LAMBERT | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - Marseille - France | Brice CHANEZ | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
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 :
1. 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
2. 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 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
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.
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 :
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:
1. Whole brain radiation therapy or stereotactic brain radiation therapy <14 days
2. 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.
3. 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
4. Major surgery (excluding placement of vascular access) < 28 days
5. Live virus and live-attenuated vaccination <28 days
6. Systemic steroid therapy or other immunosuppressive therapy < 7 days.
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:
1. Corrected QT interval >470 ms for females and >450 ms for males according to
Fridericia's formula (QTcF) assessed by ECG
2. LVEF <50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
3. Myocardial infarction or unstable angina within 6 months
4. NYHA > class II within 6 months
5. Clinically significant pericardial effusion as determined by an ECHO or MUGA
scan
6. 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, curatorship, judicial protection, family habilitation
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.
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 :
1. 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
2. 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 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
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.
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 :
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:
1. Whole brain radiation therapy or stereotactic brain radiation therapy <14 days
2. 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.
3. 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
4. Major surgery (excluding placement of vascular access) < 28 days
5. Live virus and live-attenuated vaccination <28 days
6. Systemic steroid therapy or other immunosuppressive therapy < 7 days.
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:
1. Corrected QT interval >470 ms for females and >450 ms for males according to
Fridericia's formula (QTcF) assessed by ECG
2. LVEF <50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
3. Myocardial infarction or unstable angina within 6 months
4. NYHA > class II within 6 months
5. Clinically significant pericardial effusion as determined by an ECHO or MUGA
scan
6. 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, curatorship, judicial protection, family habilitation
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.