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

Phase 2RecruitingNCT07115043

AstraZeneca60 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma Non-small Cell Lung Cancer Squamous Cell Carcinoma (Skin)Renal Cell Carcinoma Merkel Cell Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (9)

Research Site

Grand Rapids, Michigan, United States

RECRUITING

Research Site

St Louis, Missouri, United States

RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

NOT_YET_RECRUITING

Research Site

Houston, Texas, United States

RECRUITING

Research Site

San Antonio, Texas, United States

RECRUITING

Research Site

Fairfax, Virginia, United States

NOT_YET_RECRUITING

Research Site

East Melbourne, Australia

RECRUITING

Research Site

Chūōku, Japan

RECRUITING

Research Site

Kashiwa, Japan

RECRUITING

Outcomes

Primary Outcomes

Safety- Part 1A & Part 2A (dose escalation) and Part 2B (dose expansion)

To assess the safety and tolerability, characterize the DLTs, and determine the MTD and RP2D(s) of AZD6750 as a single agent and in combination with other anti-cancer agents as specified in each respective module

Time frame: Measured from the informed consent until Day 90 post-last dose.

Efficacy- Part 2B only (dose expansion)

To assess the preliminary anti-tumor activity of AZD6750 in combination with other anti-cancer agents.

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 Outcomes

Pharmacodynamic- Part 1A & Part 2A (dose escalation) and Part B (dose expansion)

To assess immunomodulatory biomarker PD-L1 at baseline and on treatment as a single agent and in combination with other anti-cancer agents as specified in each respective module

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)

To assess the incidence of anti-drug antibodies (ADA) against AZD6750 in serum and in combination with other anti-cancer agents as specified in each respective module

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)

To assess the preliminary anti-tumor activity of AZD6750 alone and in combination with other anti-cancer agents.

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)

To assess the plasma concentration of AZD6750 as a single agent and in combination with other anti-cancer agents as specified in each respective module. Each cycle is 28 days or 21 days depending on Module/dosing schedule)