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

Purpose

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

Conditions

  • Melanoma
  • Non-small Cell Lung Cancer
  • Squamous Cell Carcinoma (Skin)
  • Renal Cell Carcinoma
  • Merkel Cell Carcinoma
  • Triple Negative Breast Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Gastric Cancer/Gastroesophageal Junction Cancer
  • High Grade Serous Ovarian Carcinoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Module 1 consists of treatment with AZD6750 administered as a single agent to enroll participants with select locally advanced or metastatic solid tumors who have received prior adequate SoC. Select solid tumors include the tumor types known to show activity with ICIs (either as a single agent or in combination with other anti-cancer agents) or include reports potentially showing benefit of IL-2. Module 1 will consist of Part 1A (dose escalation). The combination arm (Module 2) will open on agreement with SRC, and will investigate AZD6750 and rilvegostomig, enrolling participants with Stage IV NSCLC who either received at least one line of therapy in metastatic setting or are treatment naïve in metastatic setting and have a PD-L1 expression ≥ 1%. Module 2 will consist of an escalation arm (Module 2A) and an expansion arm (Module 2B). Dose expansion (Module 2B) may open further to characterize preliminary efficacy of AZD6750 in combination with rilvegostomig.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Module 1 		AZD6750 administered intravenously (IV) as a single agent
  • Drug: AZD6750
    AZD6750- CD8 guided IL-2
Experimental
Module 2 		AZD6750 given in combination with rilvegostomig (IV)
  • Drug: AZD6750
    AZD6750- CD8 guided IL-2
  • Drug: rilvegostomig
    Rilvegostomig- PD1-TIGIT bispecific antibody

Recruiting Locations

Research Site
Grand Rapids, Michigan 49546

Research Site
St Louis, Missouri 63110

Research Site
Pittsburgh, Pennsylvania 15232

Research Site
Houston, Texas 77030

Research Site
San Antonio, Texas 78229

Research Site
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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