Detailed Description
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
Eligibility Criteria
Age Range: 18 years to No maximum
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
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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