A Study of ASP3082 in Adults With Advanced Solid Tumors

Inclusion Criteria:

• Participant has locally advanced (unresectable) or metastatic solid tumor malignancywith documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation andhas received prior standard therapy and the investigator does not see any furtherclinical benefit from continuing such targeted therapy, or is ineligible to receiveor has refused standard approved therapies (no limit to the number of priortreatment regimens).

• For the ASP3082 monotherapy escalation cohorts, participants with solid tumormalignancies are allowed to be enrolled.

• For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX: Participant must havemPDAC that has not been previously treated with chemotherapy. If a participantreceived (neo)adjuvant therapy, tumor recurrence or disease progression must haveoccurred at least 6 months after completing the last dose of the (neo)adjuvanttherapy.

• Participant consents to provide tumor specimen in a tissue block or unstained serialslides or a tumor biopsy (core needle biopsy or excision) obtained after the lastinterventional treatment, but not more than 56 days prior to start of studyintervention. Participant also consents to provide a sample for tumor biopsy duringthe treatment period as indicated in the study protocol. If a participant cannotprovide a fresh tissue biopsy sample, the site should consult with the sponsor/studymedical monitor.

• Participant has at least 1 measurable lesion per Response Evaluation Criteria inSolid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area areconsidered measurable if progression has been demonstrated in such lesions.

• Participant has an ECOG performance status of 0, 1 or 2 for dose escalation, and 0or 1 for dose expansion.

• Participant's last dose of prior antineoplastic therapy, including anyimmunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior toinitiation of study intervention administration.

• Participant has completed any radiotherapy (including stereotactic radiosurgery) atleast 14 days prior to the start of study intervention administration. Participantsmust have recovered from all radiation-related toxicities, not requirecorticosteroids (NOTE: Physiologic replacement dose of hydrocortisone or itsequivalent [defined as up to 30 mg per day of hydrocortisone, 2 mg per day ofdexamethasone, or up to 10 mg per day of prednisone] is permitted), and not haveactive 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 haveimproved to grade 1 or baseline within 14 days prior to start of study intervention.

• Participant has adequate organ function as indicated by protocol laboratory valueparameters (If a participant has received a recent blood transfusion, the laboratorytests must be obtained >= 14 days after any blood transfusion.).

• Female participant is not pregnant, confirmed by pregnancy test and medicalevaluation 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 informedconsent through at least 6 months after study intervention administration.

• Female participant must agree not to breastfeed starting at screening and throughoutthe study period and for 6 months after study intervention administration.

• Female participant must not donate ova starting at first dose of study interventionand throughout the study period and for 6 months after study interventionadministration.

• Male participant with female partner(s) of childbearing potential (includingbreastfeeding partner) must agree to use contraception throughout the treatmentperiod and for 3 months after study intervention administration.

• Male participant must not donate sperm during the treatment period and for 3 monthsafter study intervention administration.

• Male participant with pregnant partner(s) must agree to remain abstinent or use acondom for the duration of the pregnancy throughout the study period and for 3months after study intervention administration.

• Participant agrees not to participate in another interventional study whilereceiving study intervention (Participants who are currently in the follow-up periodof 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 orintervention) within the previous 2 years, except for local malignancies that havebeen apparently cured, such as basal or squamous cell skin cancer, superficialbladder cancer or carcinoma in situ of the cervix or breast, which are allowed.

• Participant has a known or suspected hypersensitivity to ASP3082 or any componentsof the formulation used.

• Participant with active hepatitis B (including acute hepatitis B virus [HBV] orchronic HBV) or hepatitis C virus [HCV] (ribonucleic acid [RNA] detected byqualitative assay). HCV RNA testing is not required in participants with negativeHCV antibody testing.

• Participant has a known history of human immunodeficiency virus [HIV] infection. NoHIV testing is required unless mandated by a local health authority.

• Participant has had a myocardial infarction or unstable angina within 6 months priorto the start of study intervention, left ventricular ejection fraction (LVEF) < 50%as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) orcurrently has an uncontrolled illness including, but not limited to symptomaticcongestive heart failure, clinically significant cardiac disease, unstable anginapectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QTsyndrome.

• Participant has a corrected QT interval (single electrocardiogram [ECG]) usingFridericia's formula (QTcF) > 450 milliseconds (msec) (men) or >470 msec (women)during screening.

• Participant has received prior treatment with a specific KRAS G12Dinhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D. Participantswho received prior treatment with a KRAS G12D inhibitor/degrader are eligible forthe ASP3082 combination therapy cohort.

• Participant has an active infection requiring intravenous antibiotics within 14 daysprior to study intervention.

• Participant is expected to require another form of antineoplastic therapy while onstudy treatment.

• Participant has any condition which makes the participant unsuitable for studyparticipation (such as psychiatric illness/social situations that would limitcompliance with study requirements).

• Participant has had major surgery within 4 weeks prior to first dose of studyintervention.

For ASP3082 Combination Therapy:

• Prior discontinuation of cetuximab treatment due to toxicity or intolerance ofcetuximab.

• History of interstitial lung disease requiring systemic steroid treatment. Note thata participant with resolved pulmonary infections or radiation pneumonitis iseligible.