Volrustomig Priming Regimens Exploratory Phase II Platform Study
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06448754
- Lead Sponsor
- AstraZeneca
- Brief Summary
Purpose of this study is to assess the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of volrustomig in combination with other anticancer drugs in participants with specified solid tumors.
- Detailed Description
This Phase II, platform, open-label, multicenter study will evaluate the efficacy, safety, and tolerability of volrustomig in combination with anticancer drugs in various solid tumor types.
This platform study currently includes 2 substudies:
Substudy 1: metastatic non-small cell lung cancer (mNSCLC) (non-squamous \[NSQ\]). Participants will be randomized in two treatment arms: Arm 1A and Arm 1B.
Substudy 2: mNSCLC (squamous \[SQ\] or NSQ). Participants will enroll to the Arm 2A only.
All arms will test a volrustomig dosing in combination with chemotherapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration.
- Life expectancy greater than or equal to (>=) 12 weeks.
- Adequate organ and bone marrow function.
- Body weight greater than (>) 35 kilograms (kg) at screening and at randomization.
- Histologically or cytologically documented NSQ NSCLC in substudy 1 and SQ or NSQ mNSCLC in substudy 2.
- Absence of sensitizing epidermal growth factor receptor (EGFR) mutations.
- Absence of documented tumor genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies.
- At least one measurable lesion not previously irradiated that can be accurately measured at baseline as >= 10 millimeter (mm) in the longest diameter.
Key
- Spinal cord compression.
- History of primary active immunodeficiency.
- Active or prior documented autoimmune or inflammatory disorders.
- Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant.
- Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of radiation therapy and study enrollment.
- Prior chemotherapy or any other systemic therapy for Stage IV NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for local disease are eligible, provided that progression has occurred greater (>) 12 months from end of last therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1: Arm 1A: Volrustomig dose regimen 1 + Carboplatin and Pemetrexed Volrustomig Volrustomig priming dose followed by volrustomig dosing regimen 1 in combination with carboplatin and pemetrexed. Substudy 1: Arm 1A: Volrustomig dose regimen 1 + Carboplatin and Pemetrexed Carboplatin Volrustomig priming dose followed by volrustomig dosing regimen 1 in combination with carboplatin and pemetrexed. Substudy 1: Arm 1A: Volrustomig dose regimen 1 + Carboplatin and Pemetrexed Pemetrexed Volrustomig priming dose followed by volrustomig dosing regimen 1 in combination with carboplatin and pemetrexed. Substudy 1: Arm 1B: Volrustomig dose regimen 2 + Carboplatin and Pemetrexed Volrustomig Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with carboplatin and pemetrexed. Substudy 1: Arm 1B: Volrustomig dose regimen 2 + Carboplatin and Pemetrexed Carboplatin Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with carboplatin and pemetrexed. Substudy 1: Arm 1B: Volrustomig dose regimen 2 + Carboplatin and Pemetrexed Pemetrexed Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with carboplatin and pemetrexed. Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Volrustomig Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel). Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Carboplatin Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel). Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Pemetrexed Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel). Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Ramucirumab Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel). Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel Paclitaxel Volrustomig priming dose + ramucirumab + histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel).
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) From screening (Days -28 to Day -1) up to 2 year 10 months The safety and tolerability of volrustomig in combination with other anticancer drugs in participants with specified solid tumors will be assessed.
Confirmed Objective Response rate (ORR) Up to 2 year 10 months ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) Up to 2 year 10 months DCR is defined as the percentage of participants who have a CR or PR or who have stable disease (SD) after the date of randomization or first dose.
Duration of Response (DOR) Up to 2 year 10 months DOR is defined as the time from the date of first documented response until the date of documented progression or death due to any cause (in the absence of progression).
Progression Free Survival (PFS) Up to 2 year 10 months PFS is defined as the time from randomization or first dose until radiological progression or death due to any cause (in the absence of progression).
Overall Survival (OS) Up to 2 year 10 months OS is defined as the time from randomization or first dose until the date of death due to any cause.
Serum Concentration of Volrustomig Up to 2 year 10 months The serum concentrations volrustomig alone and when used in combination with other anticancer agents in participants with pre-specified solid tumors will be assessed.
Trough concentration (Ctrough) Up to 2 year 10 months The trough concentrations volrustomig alone and when used in combination with other anticancer agents in participants with pre-specified solid tumors will be assessed.
Maximum Observed Concentration (Cmax) Up to 2 year 10 months The serum concentrations volrustomig alone and when used in combination with other anticancer agents in participants with pre-specified solid tumors will be assessed.
Area Under the Curve (AUC) Up to 2 year 10 months The AUC concentrations of volrustomig alone and when used in combination with other anticancer agents in participants with pre-specified solid tumors will be assessed.
Number of Participants with Positive Antidrug Antibodies (ADAs) Up to 2 year 10 months The incidence of ADAs against volrustomig or other anticancer agents in serum will be assessed.
Trial Locations
- Locations (1)
Research Site
🇨🇳Taipei, Taiwan
Research Site🇨🇳Taipei, Taiwan