Part A1 dose escalation and A2 dose optimization: Participants must meet all of the following criteria:
Have a histologic or cytologic diagnosis of unresectable or metastatic solid tumor malignancy.
Have previously received at least one prior therapy targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and/or another T-cell co-stimulatory or immune checkpoint pathway, in any treatment setting (including neoadjuvant or adjuvant).
Have received prior SOC therapy appropriate for their disease type and stage and have no remaining available treatment options with established clinical benefit; or, in the opinion of the investigator, are unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy; or have declined SOC therapy.
Participants must have demonstrated radiographic progression and have at least 1 measurable lesion per RECIST v1.1 that has not been previously irradiated or has demonstrated progression of disease since radiation therapy.
ECOG PS 0 or 1 or equivalent. Participants with ECOG PS 2 may be considered upon discussion with the Sponsor Medical Monitor.
Participants with adequate organ function.
You may not be if
Active brain metastases (new lesions identified on imaging, existing lesions showing progression per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)/imaging characteristics or by clinical criteria, lesions requiring active interventions for symptom control).
Carcinomatous meningitis.
Known or suspected hypersensitivity to ARV-6723 or pembrolizumab or any of its excipients.
Active autoimmune disease or history of autoimmune diseases that may relapse.
History of severe immune-related adverse events (irAE) attributed to prior anti-PD-1/anti-CTLA-4/anti-LAG-3 therapy.
Prior treatment with any HPK1-targeting agent
Systemic anti-cancer therapy or radiation therapy within 14 days prior to study treatment start.
Current use of any prohibited concomitant medication(s) or herbal supplements which cannot be discontinued, prior to start of study intervention and for the duration of the study.
Baseline (screening) standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
