A Study of ASP3082 in Adults With Advanced Solid Tumors

NCT ID: NCT05382559

Last Updated: 2025-09-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

651 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-08

Study Completion Date

2026-10-31

Brief Summary

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This is an open-label study. This means that people in this study and clinic staff will know that they 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.

Detailed Description

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Conditions

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Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ASP3082 Dose Escalation (Monotherapy Part 1)

Participants will receive ASP3082 in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

ASP3082 Dose Expansion (Monotherapy Part 2)

Participants will receive ASP3082 with dose level(s) selected from dose escalation (part 1) in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

ASP3082 + Cetuximab Dose Escalation (Combination Therapy Part 1)

Participants will receive ASP3082 in a 21-day cycle. Cetuximab will be administered weekly.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Cetuximab

Intervention Type DRUG

Intravenous Infusion

ASP3082 + Cetuximab Dose Expansion (Combination Therapy Part 2)

Participants will receive ASP3082 or ASP3082 + Cetuximab with dose level(s) selected from dose escalation (part 1) in a 21-day cycle. Cetuximab will be administered weekly.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Cetuximab

Intervention Type DRUG

Intravenous Infusion

ASP3082 China Safety Cohort

Participants will receive ASP3082 with dose level selected from dose escalation (Monotherapy part 1) in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Treatment naive PDAC cohort ASP3082 + FOLFIRINOX

Upon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with FOLFIRINOX (leucovorin \[LV\]/fluorouracil \[5-FU\]/irinotecan/oxaliplatin) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Leucovorin

Intervention Type DRUG

Intravenous Infusion

Oxaplatin

Intervention Type DRUG

Intravenous Infusion

Fluorouracil

Intervention Type DRUG

Intravenous Infusion

Irinotecan

Intervention Type DRUG

Intravenous Infusion

Treatment naive PDAC cohort ASP3082 + Nab-Paclitaxel + Gemcitabine

Upon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with Nab-P + GEM (nanoparticle albumin-bound-paclitaxel plus gemcitabine) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Nanoparticle albumin-bound-paclitaxel

Intervention Type DRUG

Intravenous Infusion

Gemcitabine

Intervention Type DRUG

Intravenous Infusion

ASP3082 + Docetaxel - NSCLC

Participants with KRAS G12D mutant will receive ASP3082 in combination with docetaxel in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Docetaxel

Intervention Type DRUG

Intravenous Infusion

ASP3082 + Pembrolizumab - NSCLC

Participants with KRAS G12D mutant will receive ASP3082 in combination with pembrolizumab in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Pembrolizumab

Intervention Type DRUG

Intravenous Infusion

ASP3082 + (Cisplatin or Carboplatin) and Pemetrexed +/- Pembrolizumab - NSCLC

Participants with KRAS G12D mutant will receive ASP3082 in combination with platinum-based chemotherapy (cisplatin or carboplatin) and pemetrexed, with or without pembrolizumab in a 21-day cycle.

Group Type EXPERIMENTAL

ASP3082

Intervention Type DRUG

Intravenous Infusion

Pembrolizumab

Intervention Type DRUG

Intravenous Infusion

Cisplatin

Intervention Type DRUG

Intravenous Infusion

Carboplatin

Intervention Type DRUG

Intravenous Infusion

Pemetrexed

Intervention Type DRUG

Intravenous Infusion

Interventions

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ASP3082

Intravenous Infusion

Intervention Type DRUG

Cetuximab

Intravenous Infusion

Intervention Type DRUG

Leucovorin

Intravenous Infusion

Intervention Type DRUG

Oxaplatin

Intravenous Infusion

Intervention Type DRUG

Fluorouracil

Intravenous Infusion

Intervention Type DRUG

Irinotecan

Intravenous Infusion

Intervention Type DRUG

Nanoparticle albumin-bound-paclitaxel

Intravenous Infusion

Intervention Type DRUG

Gemcitabine

Intravenous Infusion

Intervention Type DRUG

Docetaxel

Intravenous Infusion

Intervention Type DRUG

Pembrolizumab

Intravenous Infusion

Intervention Type DRUG

Cisplatin

Intravenous Infusion

Intervention Type DRUG

Carboplatin

Intravenous Infusion

Intervention Type DRUG

Pemetrexed

Intravenous Infusion

Intervention Type DRUG

Eligibility Criteria

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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 or has refused 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.
* For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX: 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 not more than 56 days 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.
* 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.
* 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.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

UCLA Santa Monica Hematology Oncology

Santa Monica, California, United States

Site Status RECRUITING

Denver HealthONE Drug Development Unit

Denver, Colorado, United States

Site Status RECRUITING

Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

University of Florida, Davis Cancer Center

Gainesville, Florida, United States

Site Status RECRUITING

Florida Cancer Specialist

Lake Mary, Florida, United States

Site Status RECRUITING

Florida Cancer Specialists & Research Institute Sarasota

Sarasota, Florida, United States

Site Status RECRUITING

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Columbia University - Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Case Western

Cleveland, Ohio, United States

Site Status RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status TERMINATED

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

NEXT Oncology

San Antonio, Texas, United States

Site Status RECRUITING

NEXT Oncology - Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

University of Wisconsin Hospital

Madison, Wisconsin, United States

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Fudan University Shanghai Cancer Center

Xuhui District, Shanghai Municipality, China

Site Status RECRUITING

Site FR33003

La Tronche, Grenobele, France

Site Status RECRUITING

Site FR33002

Bordeaux, , France

Site Status RECRUITING

Site FR33001

Lyon, , France

Site Status RECRUITING

Site FR33005

Lyon, , France

Site Status RECRUITING

Site FR33004

Villejuif, Île-de-France Region, France

Site Status RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status RECRUITING

Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status RECRUITING

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status RECRUITING

Kindai University Hospital

Sayama, Osaka, Japan

Site Status RECRUITING

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan

Site Status RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Site Status RECRUITING

Yamaguchi University Hospital

Ube, Yamaguchi, Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, , Japan

Site Status RECRUITING

Site KR82002

Seongnam-si, Gyeonggi-do, South Korea

Site Status RECRUITING

Site KR82001

Jongno -Gu, Seoul, South Korea

Site Status RECRUITING

Site KR82003

Seodaemun-gu, Seoul, South Korea

Site Status RECRUITING

Site KR82004

Songpa-gu, Seoul, South Korea

Site Status RECRUITING

Site ES34001

Barcelona, , Spain

Site Status RECRUITING

Site ES34004

Madrid, , Spain

Site Status RECRUITING

Site ES34002

Málaga, , Spain

Site Status RECRUITING

Site ES34003

Seville, , Spain

Site Status RECRUITING

Countries

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United States China France Japan South Korea Spain

Central Contacts

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Astellas Pharma Inc.

Role: CONTACT

800-888-7704

Other Identifiers

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jRCT2031220738

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20250465

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-501590-39-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

3082-CL-0101

Identifier Type: -

Identifier Source: org_study_id

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