A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors

A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors

A Phase I/II Open-label Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD6750, a CD8 Guided IL-2 Agent Alone and in Combination With Other Anti-cancer Agents in Participants with Select Advanced or Metastatic Solid Tumors

Inclusion criteria: * Participant ≥ 18 year * ECOG PS of 0 to 1 * Provision of 'archival' tumor specimen * At least one measurable lesion according to RECIST v1.1, * Minimum life expectancy of 12 weeks * Adequate and stable cardiac function * Adequate bone marrow, liver and kidney function * Body weight ≥ 35 kg * Capable of giving signed informed consent Module 1 specific inclusion criteria: • Participants with locally advanced or metastatic select solid tumors (MM, Squamous cell carcinoma of skin, MCC, NSCLC, Head and neck squamous cell carcinoma, Gastric cancer/gastroesophaegeal junction cancer, RCC, HGSOC, Triple negative breast cancer) who have received adequate SoC Module 2 specific inclusion criteria: * Participants with Stage IV NSCLC Dose Escalation/Backfills 1. Have received at least one prior regimen in metastatic setting (2L+ NSCLC). Participants with actionable tumor alterations should have received targeted therapy if locally available OR 2. Have not received systemic therapy (1L NSCLC) and have PD-L1 expression ≥ 1%. Dose Expansion <!-- --> 1. Have not received systemic therapy (1L NSCLC) and have PD-L1 expression ≥ 1%. Exclusion criteria: * Any evidence of: Severe or uncontrolled systemic diseases including respiratory, cardiac or tumor-related conditions * History or planned organ or allogeneic stem cell transplantation. * Active or prior documented autoimmune or inflammatory disorders, within the past 3 years * Any prior toxicities that led to permanent discontinuation of prior immunotherapy * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy * Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids * Acute untreated or symptomatic malignant spinal cord compression, or a history of leptomeningeal carcinomatosis. * Active uncontrolled or chronic infection of hepatitis B, hepatitis C * Prior history of Grade ≥ 3 non-infectious pneumonitis. * Participant requires chronic immunosuppressive therapy (including steroids \> 10 mg prednisone/day or equivalent). * Receipt of live attenuated vaccine within 30 days. Module 2 specific exclusion criteria: * Previous treatment with anti-TIGIT therapy * 1L NSCLC participants with genetic alteration such as EGFR that has a targeted therapy in 1L as per local SoC