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RecruitingInterventionalPhase 1

A Phase 1 Study of ASP3082 in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation

NCT ID: NCT05382559Sponsor: Astellas Pharma IncLast updated: 2026-04-14

Summary

This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP3082. The study aims to check how safe and well-tolerated ASP3082 is for people with advanced solid tumors that have a specific mutation called KRAS G12D. This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP3082 by itself, or together with cetuximab. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP3082, by itself or together with cetuximab, to use in Part 2 of the study. The first group will receive the lowest dose of ASP3082. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP3082. The panel will do this for each group until all groups have received ASP3082 (by itself or together with cetuximab) or until suitable doses have been selected for Part 2. In Part 2, ASP3082 will be given in by itself, or in combination with the other study treatments. Study treatments will be given through a vein. This is called an infusion. Each treatment cycle is 21 or 28 days long. They will continue treatment until: they have medical problems from the treatment they can't tolerate; their cancer gets worse; they start other cancer treatment; or they ask to stop treatment.

Arms & interventions

  • DrugSetidegrasib

    Intravenous Infusion

  • DrugCetuximab

    Intravenous Infusion

  • DrugLeucovorin

    Intravenous Infusion

  • DrugOxaliplatin

    Intravenous Infusion

  • DrugFluorouracil

    Intravenous Infusion

  • DrugIrinotecan

    Intravenous Infusion

  • DrugNanoparticle albumin-bound-paclitaxel

    Intravenous Infusion

  • DrugGemcitabine

    Intravenous Infusion

  • DrugDocetaxel

    Intravenous Infusion

  • DrugPembrolizumab

    Intravenous Infusion

  • DrugCisplatin

    Intravenous Infusion

  • DrugCarboplatin

    Intravenous Infusion

  • DrugPemetrexed

    Intravenous Infusion

  • DrugLiposomal Irinotecan

    Intravenous Infusion

Outcome measures

Primary

  • Incidence of Dose Limiting Toxicities (DLTs)

    A DLT is defined as any event meeting the DLT criteria excluding toxicities clearly related to disease progression or intercurrent illness or standard of care (SoC) regimens as determined by the investigator.

    Time frame: Up to 28 Days

  • Number of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures.

    Time frame: Up to 48 months

  • Number of Participants with Serious Adverse Events (SAEs)

    An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important events.

    Time frame: Up to 48 months

  • Number of Participants with laboratory value abnormalities and/or adverse events (AEs)

    Number of participants with potentially clinically significant laboratory values.

    Time frame: Up to 48 months

  • Number of Participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs)

    Number of participants with potentially clinically significant ECG values.

    Time frame: Up to 48 months

  • Number of Participants with vital sign abnormalities and/or adverse events (AEs)

    Number of participants with potentially clinically significant vital sign values.

    Time frame: Up to 48 months

  • Number of Participants with physical exam abnormalities and/or adverse events

    Number of participants with potentially clinically significant physical exam values.

    Time frame: Up to 48 months

  • Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status

    The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

    Time frame: Up to 48 months

Secondary

  • Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Time frame: Up to 48 months

  • Duration of Response (DOR) per RECIST v 1.1

    Time frame: Up to 48 months

  • Disease Control Rate (DCR) per RECIST v 1.1

    Time frame: Up to 48 months

  • Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)

    Time frame: Up to 48 months

  • PK of ASP3082 in plasma: Maximum Concentration (Cmax)

    Time frame: Up to 48 months

  • PK of ASP3082 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)

    Time frame: Up to 48 months

  • PK of ASP3082 in plasma: Time of maximum concentration (tmax)

    Time frame: Up to 48 months

  • Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples

    Time frame: Up to 48 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog \[KRAS\] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive standard approved therapies (no limit to the number of prior treatment regimens). * For the ASP3082 monotherapy escalation cohorts, participants with solid tumor malignancies are allowed to be enrolled. Participants with other known KRAS G12 mutations will not be eligible for the study * For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX or NALRIFOX: Participant must have mPDAC that has not been previously treated with chemotherapy. If a participant received (neo)adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the (neo)adjuvant therapy. * Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a tumor biopsy (core needle biopsy or excision) obtained after the last interventional treatment, but prior to start of study intervention. Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the study protocol. If a participant cannot provide a fresh tissue biopsy sample, the site should consult with the sponsor/study medical monitor. * Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Participant has an ECOG performance status of 0, 1 or 2 for dose escalation, and 0 or 1 for dose expansion. * Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of study intervention administration. * Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of study intervention administration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids (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), and not have active radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<= 2 weeks of radiotherapy) to non-central nervous system disease. * Participant's adverse events \[AEs\] (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of study intervention (or prior to staring SoC chemotherapy, for first line (1L) participants receiving Nab-P+GEM FOLFIRINOX or NALIRIFOX. * Participant has adequate organ function as indicated by protocol laboratory value parameters (If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 14 days after any blood transfusion.). * Female participant is not pregnant, confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP). * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after study intervention administration. * EU only: For combination therapy with carboplatin, follow contraception guidelines from the time of informed consent through at least 7 months after the final dose of carboplatin. * South Korea only: For combination therapy with oxaliplatin, follow contraception guidelines from the time of informed consent through at least 15 months after the final dose of oxaliplatin. For combination therapy with cisplatin, follow contraception guidelines from the time of informed consent through at least 14 months after the final dose of cisplatin. * Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after study intervention administration. * Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for 6 months after study intervention administration. * Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after study intervention administration. * Male participant must not donate sperm during the treatment period and for 3 months after study intervention administration. * South Korea only: For combination therapy with oxaliplatin, follow contraception guidelines from the time of informed consent through at least 12 months after the final dose of oxaliplatin. For combination therapy with cisplatin, follow contraception guidelines from the time of informed consent through at least 11 months after the final dose of cisplatin. * Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after study intervention administration. * Participant agrees not to participate in another interventional study while receiving study intervention (Participants who are currently in the follow-up period of an interventional clinical trial are allowed). Exclusion Criteria: * Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of study intervention. * Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible. * Participant has leptomeningeal disease as a manifestation of the current malignancy. * Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed. * Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used. * Participant with active hepatitis B (including acute hepatitis B virus \[HBV\] or chronic HBV) or hepatitis C virus \[HCV\] (ribonucleic acid \[RNA\] detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing. * Participant has a known history of human immunodeficiency virus \[HIV\] infection. No HIV testing is required unless mandated by a local health authority. * Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention, left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QT syndrome. * Participant has a corrected QT interval (single electrocardiogram \[ECG\]) using Fridericia's formula (QTcF) \> 450 milliseconds (msec) (men) or \>470 msec (women) during screening. * Participant has received prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D. Participants who received prior treatment with a KRAS G12D inhibitor/degrader are eligible for the ASP3082 combination therapy cohort. * Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention. * Participant is expected to require another form of antineoplastic therapy while on study treatment. * Participant has any condition which makes the participant unsuitable for study participation (such as psychiatric illness/social situations that would limit compliance with study requirements). * Participant has had major surgery within 4 weeks prior to first dose of study intervention. For ASP3082 Combination Therapy: * Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab. * History of interstitial lung disease requiring systemic steroid treatment. Note that a participant with resolved pulmonary infections or radiation pneumonitis is eligible.

Study locations (23)

City of Hope National Medical Center

Duarte, California, 91010

Recruiting

UCLA Santa Monica Hematology Oncology

Santa Monica, California, 90404

Recruiting

Denver HealthONE Drug Development Unit

Denver, Colorado, 80218

Recruiting

Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, 06520-8028

Recruiting

Georgetown University Hospital

Washington D.C., District of Columbia, 20007

Recruiting

University of Florida, Davis Cancer Center

Gainesville, Florida, 32610

Recruiting

Florida Cancer Specialist

Lake Mary, Florida, 32746

Recruiting

Florida Cancer Specialists & Research Institute Sarasota

Sarasota, Florida, 34232-6422

Recruiting

University of Kansas Medical Center

Westwood, Kansas, 66205

Recruiting

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Trinity Health Ann Arbor Hospital

Ypsilanti, Michigan, 48197

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting

Roswell Park Cancer Institute

Buffalo, New York, 14263

Recruiting

Columbia University - Herbert Irving Comprehensive Cancer Center

New York, New York, 10032

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting

Case Western

Cleveland, Ohio, 44106

Recruiting

Oregon Health and Science University

Portland, Oregon, 97239

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Terminated

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

Recruiting

NEXT Oncology

San Antonio, Texas, 78229

Recruiting

NEXT Oncology - Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

University of Wisconsin Hospital

Madison, Wisconsin, 53792

Recruiting

References

  • Park W, Kasi A, Spira AI, Paz-Ares Rodriguez L, Herzberg BO, Pelster MS, Tolcher AW, Kuboki Y, Kitano S, Shoji H, Wang JS, Berlin JD, Hollebecque A, LoRusso P, Fountzilas C, Cassier PA, Nishina T, Sakai D, Inagaki C, Morgensztern D, Ueno M, Jung M, Kim SW, Janne PA, Italiano A, You B, Macarulla T, Fujii H, Shetty A, Lu Y, Cui D, Kadam S, Gill SC, Toyoshima J, Saito T, Goldman JW. Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer. N Engl J Med. 2026 Apr 9;394(14):1409-1420. doi: 10.1056/NEJMoa2600752. Epub 2026 Mar 25.(PubMed)