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

Primary Outcome Measures  :

1. Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 21 Days ]A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness.
   
2. Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 48 months ]

   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.
   

3. Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 48 months ]

   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.
   

4. Number of Participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]Number of participants with potentially clinically significant laboratory values.
   
5. Number of Participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]Number of participants with potentially clinically significant ECG values.
   
6. Number of Participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]Number of participants with potentially clinically significant vital sign values.
   
7. Number of Participants with physical exam abnormalities and/or adverse events [ Time Frame: Up to 48 months ]Number of participants with potentially clinically significant physical exam values.
   
8. Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 48 months ]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.

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 progressed after receiving all available standard approved therapies (no limit to the number of prior treatment regimens). If KRAS mutation status is unknown, an archival tumor sample can be sent to the central lab during the prescreening/screening period.
• 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 investigational product (IP). Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the Schedule of Assessments.
• 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.
• 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 IP administration.
• Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of IP 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 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 IP.
• 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 >= 28 days after any blood transfusion.).
• Female participant is not pregnant 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 IP administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after IP administration.
• Female participant must not donate ova starting at first dose of IP and throughout the study period and for 6 months after IP 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 IP administration.
• Male participant must not donate sperm during the treatment period and for 3 months after IP 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 IP administration.
• Participant agrees not to participate in another interventional study while receiving IP (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 IP.
• Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible if they have been off corticosteroids and antiepileptic drugs for at least 14 days prior to start of IP.
• 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 known history of positive hepatitis B surface antigen or isolated hepatitis B core antibody (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 IP or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome, or right bundle branch block with left anterior hemiblock (bifascicular block).
• Participant has a corrected QT interval (single electrocardiogram [ECG]) using Fridericia's formula (QTcF) > 450 milliseconds (msec) during screening. ECGs will be performed in triplicate during screening.
• Participant has received prior treatment with a specific KRAS G12D inhibitor.
• Participant has an infection requiring systemic therapy (e.g., intravenous antibiotics) within 14 days prior to IP.
• 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 known history of COVID-19 positive polymerase chain reaction (PCR) test within 4 weeks prior to the start of study treatment.
• Participant has had major surgery within 4 weeks prior to first dose of IP.