A study of ASP3082 in adults with previously treated solid tumors

JRCT ID: jRCT2031220738

Registered date:27/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid Tumor
• Date of first enrollment: 22/06/2023
• Target sample size: 541
• Countries of recruitment: United states,Japan
• Study type: Interventional

Intervention(s)

This study will be in 2 parts.
-ASP3082 Dose Escalation (Part 1)
Different small groups of people will receive lower to higher doses of ASP3082, by itself or together with cetuximab.

-ASP3082 Dose Expansion (Part 2)
Other different small groups of people will receive ASP3082, by itself or together with cetuximab or chemotherapy, with the most suitable doses worked out from Part 1. ASP3082 (cetuximab or chemotherapy if used) will be given through a vein. This is called an infusion.

Each treatment cycle for ASP3082 is 21 or 28 days long. Cetuximab will be administered weekly. People 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.

Outcome(s)

Primary Outcome

-Dose Limiting Toxicities (DLTs)
-Adverse Events (AEs)
-Serious Adverse Events (SAEs)
-Clinical laboratory values
-Routine 12-lead electrocardiogram
-Vital sign
-Physical exam
-ECOG performance status score

Secondary Outcome

-Objective Response Rate (ORR) per RECIST v1.1
-Duration of Response (DOR) per RECIST v1.1
-Disease Control Rate (DCR) per RECIST v1.1
-Pharmacokinetics (PK) parameters of ASP3082 in plasma: Area under the concentration-time curve (AUC), Maximum concentration (Cmax), Concentration immediately prior to dosing at multiple dosing (Ctrough), Time of maximum concentration (tmax)
-Changes in KRAS G12D level in tumor samples

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 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.
2. 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.
3. 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.
4. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 for dose escalation, and 0 or 1 for dose expansion.
5. 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.
6. 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 had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<= 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
7. 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.
8. 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).
9. Female participant is not pregnant, confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply:
o Not a woman of childbearing potential (WOCBP).
o WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after study intervention administration.
10. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after study intervention administration.
11. 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.
12. 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.
13. Male participant must not donate sperm during the treatment period and for 3 months after study intervention administration.
14. 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.
15. 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).

Exclude criteria

1. Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of study intervention.
2. Participant has symptomatic or untreated CNS metastases. Participants with asymptomatic, treated CNS metastases are eligible.
3. Participant has leptomeningeal disease as a manifestation of the current malignancy.
4. 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.
5. Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used.
6. 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.
7. Participant has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by a local health authority.
8. 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.
9. Participant has a corrected QT interval (single electrocardiogram [ECG]) using Fridericia's formula (QTcF) > 450 milliseconds (msec) (men) or >470 msec (women) during screening.
10. 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.
11. Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention.
12. Participant is expected to require another form of antineoplastic therapy while on study treatment.
13. 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).
14. Participant has known history of COVID-19 positive polymerase chain reaction (PCR) test within 4 weeks prior to the start of study treatment.
15. Participant has had major surgery within 4 weeks prior to first dose of study intervention.
For ASP3082 Combination Therapy:
1. Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab.
2. History of interstitial lung disease requiring systemic steroid treatment. Note that a participant with resolved pulmonary infections or radiation pneumonitis is eligible.

Related Information

• Primary Sponsor: Fujii Hisaki
• Secondary ID(s): NCT05382559