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

Official title

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

Overview

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

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

Interventions

• Drug AZD6750
  AZD6750- CD8 guided IL-2
• Drug rilvegostomig
  Rilvegostomig- PD1-TIGIT bispecific antibody

Primary outcome measures

• Safety- Part 1A & Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from the informed consent until Day 90 post-last dose.]
• Efficacy- Part 2B only (dose expansion) [Time frame: Measured every 6 weeks for 48 weeks and every 12 weeks thereafter from first dose until disease progression or death in the absence of disease progression(approximately 2 years)]

Secondary outcome measures (9)

• Pharmacodynamic- Part 1A & Part 2A (dose escalation) and Part B (dose expansion) [Time frame: Measured with baseline and On-treatment biopsy. On-treatment biopsy is planned during Cycle 2 during Cycle 2 (each cycle is 28 days or 21 days depending on Module/dosing schedule)]
• Immunogenicity- Part 1A & 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose. Each cycle is 28 days or 21 days depending on Module/dosing schedule).]
• Efficacy (Part 1A and 2A) [Time frame: Measured every 6 weeks for 48 weeks and every 12 weeks thereafter thereafter from first dose until disease progression or death in the absence of disease progression (approximately 2 years)]
• PK Maximum plasma concentration (Cmax)- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]
• PK Area Under Curve (AUC)- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]
• PK Time to maximum plasma concentration (tmax)- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]
• PK Clearance- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]
• PK Half-life- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]
• PK Minimum observed concentration (Cmin)- Part 1A and Part 2A (dose escalation) and Part 2B (dose expansion) [Time frame: Measured from pre-infusion on Cycle 1 up to Day 28 post last dose on predefined intervals]

Eligibility criteria

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

• 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
• Have not received systemic therapy (1L NSCLC) and have PD-L1 expression ≥ 1%.

Dose Expansion

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• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Research Site — Grand Rapids
• Research Site — St Louis
• Research Site — Pittsburgh
• Research Site — Houston
• Research Site — San Antonio
• Research Site — Fairfax

South Korea · 4 centers

• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

Japan · 2 centers

• Research Site — Chūōku
• Research Site — Kashiwa

Australia · 1 center

• Research Site — East Melbourne

Identifiers

NCT: NCT07115043 · D7350C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗