A Study to Evaluate ARV-806 in Adults With Advanced Cancer That Has the KRAS G12D Mutation

Inclusion Criteria:

Part A:

• Histological or cytological diagnosis of unresectable or metastatic solid tumormalignancy, AND

• Must have evidence of KRAS G12D mutation in tumor tissue or blood (circulating tumordeoxyribonucleic acid [ctDNA]), AND

• Must have received prior standard-of-care (SOC) therapy appropriate for their typeand stage of disease and have no other available treatment options with curativeintent, or, in the opinion of the investigator, would be unlikely to tolerate orderive clinically meaningful benefit from appropriate SOC therapy, AND

• Must have at least 1 measurable lesion

Part B:

• Histological or cytological diagnosis of unresectable or metastatic pancreaticductal adenocarcinoma (PDAC) with KRAS G12D mutation status confirmed by localtesting of tumor tissue using a validated molecular or next-generation sequencing (NGS) testing, AND

• Must be willing to provide archival tumor tissue or willing to undergo pretreatmentbiopsy, AND

• Must have received at least one prior standard of care systemic therapy for PDAC (systemic therapy received in the neoadjuvant or adjuvant setting is allowed), AND

• Participants must have at least 1 measurable lesion

Part A / Part B:

• Eastern Cooperative Oncology Group performance status of 0 or 1,

• Participants with adequate organ function,

• Participants must accept and follow pregnancy prevention guidance.

Exclusion Criteria:

Part A / Part B:

• Active brain metastases

• Carcinomatous meningitis

• Uncontrolled hypertension despite optimal medical therapy

• Prior treatment with a KRAS G12D or a KRAS G12C targeting therapy (pan-KRASinhibitor/degrader included)

• Participants with an inability to comply with listed prohibited treatments

• Systemic anticancer therapy within 2 weeks or 5 half-lives (whichever is shorter) orradiation therapy (excluding palliative radiation) within 2 weeks prior to the studyintervention treatment. If the last immediate anticancer treatment contained anantibody-based agent(s), then an interval of 28 days or 5 half-lives (whichever isshorter) of the agent(s) is required prior to receiving the study interventiontreatment.

• Standard 12-lead electrocardiogram that demonstrates clinically relevantabnormalities that may affect participant safety or interpretation of study results