A Phase III, Two-Arm, Parallel, Randomized, Multi-Center, Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer (mNSCLC).

JRCT ID: jRCT2031230678

Registered date:06/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small Cell Lung Cancer
• Date of first enrollment: 20/10/2023
• Target sample size: 900
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,France,Japan,Germany,Japan,Hungary,Japan,Italy,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Slovakia,Japan,Republic of Korea,Japan,South Africa,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Volrustomig plus chemotherapy.
Participants in the volrustomig plus chemotherapy arm will receive 750 mg volrustomig plus histology-specific platinum based chemotherapy (see below) by intravenous (iv) infusion on Day 1 of every 3 week (21-day) cycle for 4 cycles. After the first 4 cycles, volrustomig (750 mg) will be administered on Day 1 of every 3-week (21 day) cycle.

- Control: Pembrolizumab plus chemotherapy.
Participants in the pembrolizumab plus chemotherapy arm will receive 200 mg pembrolizumab plus histology-specific platinum based chemotherapy (see below) by iv infusion every 3 weeks for 4 cycles. After the first 4 cycles, pembrolizumab (200 mg) will be administered on Day 1 of every 3-week (21-day) cycle.

All randomized participants will receive one of the following platinum-based chemotherapy regimens in combination with either volrustomig or pembrolizumab on Day 1 of every 3-week (21-day) cycle for the first 4 cycles.

- For participants with non-squamous tumours: pemetrexed (500 mg/m2) plus carboplatin (AUC 5 or 6); pemetrexed maintenance may continue Q3W.

Note: pemetrexed maintenance therapy (Q3W) is allowed until disease progression (plus a subsequent scan) or specific discontinuation criteria are met.

- For participants with squamous tumours: paclitaxel (175 to 200 mg/m2) plus carboplatin (AUC 5 or 6).

Outcome(s)

Primary Outcome

1. Progression-Free Survival (PFS) (using BICR assessments according to RECIST 1.1) [ Time Frame: Up to approximately 6 years ]
PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression), in PD-L1-negative participants.

2. Overall Survival (OS), in PD-L1-negative participants. [ Time Frame: Up to approximately 6 years ]
OS is defined as the time from randomization until the date of death due to any cause, in PD-L1-negative participants.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Histologically or cytologically documented squamous or non-squamous NSCLC.

2. Stage IV NSCLC (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology 2016), not amen
able to curative surgery or radiation.

3. Tumours with no specific abnormality of the genes.
- Sensitizing EGFR mutations and ALK and ROS1 rearrangements.

- 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 first-line therapies.

Exclude criteria

1. Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare subtypes are excluded.

2. Spinal cord compression.

3. Brain metastases unless asymptomatic and stable. Please ask the study doctor for the details.

4. History of another primary malignancy except for patients treated with curative intent. Please ask the study doctor for the details.

5. Judgement by the study doctor that the individual should not participate in the study.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT05984277