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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.