A Phase III, Randomized, Open-label, Multi Center, Global Study of Volrustomig MEDI5752 as Sequential Therapy Versus Observation in Participants with Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma, Who Have Not Progressed Following Definitive Concurrent Chemoradiotherapy
概览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,140
- 试验地点
- 14
- 主要终点
- To demonstrate the superiority of volrustomig administered after cCRT relative to observation by assessment of PFS in participants with unresected LA HNSCC with tumors with PD L1 CPS less than equal to 1
概览
简要总结
This is a Phase III, 2-arm, randomized, open-label, multi-center, global study assessing the efficacy and safety of volrustomig compared to observation in participants with unresected LA-HNSCC (tumor sites include: HPV-positive OP, HPV-negative OP, OC, HP, and LX) Stage III to IVA/B whose disease has not progressed following the completion of definitive cCRT.
Approximately 1590 participants with LA-HNSCC are planned to be screened in order to randomize approximately 1145 participants in a 1:1 ratio to one of the following arms:
· Arm A - Volrustomig: Participants in the volrustomig arm will receive 750 mg IV on
Day 1 of each 21-day cycle for up to 12 months or 18 cycles, or until RECIST 1.1‑defined radiological PD confirmed by investigator assessment, unless there is evidence of unacceptable toxicity, or if a participant requests to stop the study intervention. Approximately 573 participants will be treated with volrustomig 750 mg IV Q3W in this study.
· Arm B - Observation: Participants in the observation arm will undergo observation for up to 12 months or until RECIST 1.1-defined radiological PD confirmed by investigator assessment, or any study discontinuation criterion is met Approximately 573 participants will be observed during this study.
Randomization will be stratified according to PD-L1 expression (CPS < 1 versus CPS 1 to 19 versus CPS ≥ 20), primary tumor site/HPV status (HPV-positive OP versus HPV-negative OP versus OC/HP/LX), CTx utilized in definitive cCRT (cisplatin-based versus others), and tumor and nodal stage (< T4 and < N2c [or < N3 if HPV-positive OPC] versus T4 and/or
≥ N2c [or N3 if HPV-positive OPC]).
Recruitment of participants with expression of PD-L1 CPS < 1 will be capped at a maximum of 20% of the total randomized participants (ie, 229 participants), so that approximately
916 participants with PD-L1 CPS ≥ 1 will be randomized. Recruitment of participants with LX tumor subtype will be capped at a maximum of 15% (ie, 172 participants) of the total randomized participants.
Participants will receive study intervention for a maximum of 12 months or 18 cycles, or undergo observation for 12 months, or until RECIST 1.1‑defined radiological PD confirmed by investigator assessment, unless there is evidence of unacceptable toxicity, or if a participant requests to stop the study intervention, as applicable to the arm participants are assigned to.
Participants who discontinue study intervention for reasons other than RECIST 1.1-defined radiological PD must have post-treatment follow-up tumor assessments as per the protocol until RECIST 1.1-defined radiological PD as assessed by investigator assessment, or other study discontinuation criterion per protocol.
For all participants, central testing will be used to determine PD-L1 status (CPS < 1 versus CPS 1 to 19 versus CPS ≥ 20) prior to randomization using the PD-L1 IHC 28-8 pharmDx assay.
For participants with OPC only, documented HPV status by IHC analysis with CINtec® Histology p16 Assay. If not available at the time of screening, a tumor sample should be collected for testing at the central laboratory.
If study intervention or observation is permanently discontinued, the participant should, if possible, remain in the study. Note that discontinuation from study intervention or observation is not the same thing as a discontinuation or withdrawal from the study
Follow-up of Participants Post Discontinuation of Study Intervention (Arm A only):
After study intervention discontinuation, participants will undergo an end of treatment visit (30 days post last dose [± 7 days]) and will be followed up for safety assessments 90 days (± 7 days) after their last dose of study intervention (ie, the safety follow-up visit). Additional assessments to be performed at the time of the 90-day safety follow-up visit are detailed in the protocol SoA.
Participants who have discontinued study intervention in the absence of RECIST 1.1-defined radiological PD by investigator assessment will be followed up with tumor assessments according to the protocol SoA until RECIST 1.1-defined PD or death, regardless of whether or not the participant started a subsequent anticancer therapy, unless they have withdrawn all consent to study-related assessments.
Follow-up of Participants in the Observation Arm (Arm B only):
Participants will be followed up for survival status after PD every 12 weeks (± 7 days) until death, withdrawal of consent, or the end of the study (ie, progression/survival follow-up).
Survival information may be obtained via telephone contact with the participant or the participant’s family, or by contact with the participant’s current physician.
Participants will be followed up for survival status every 12 weeks (± 7 days) after the safety follow-up visit, as indicated in the protocol SoAs until death, withdrawal of consent, lost to follow-up, or the end of the study. Survival information may be obtained via telephone contact with the participant or the participant’s family, or by contact with the participant’s current physician. Additional assessments, including subsequent anticancer therapy, are to be recorded at the time of survival follow-up and are detailed in the SoAs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion criteria Screening Part I In order to allow for pre-cCRT tumor sample collection, Part I Screening procedures may begin before cCRT is initiated.
- •Participant must be 18 years of age, at the time of signing the ICF.
- •Histologically or cytologically documented LA squamous cell carcinoma of the OP, HP, OC, or LX with no evidence of M
- •Confirmed unresected Stage III HPV-mediated OPC, ie, T 0-3 N3 M0, or T4 N 0-3 M0; confirmed Stage IVA, IVB HPV-negative OPC/non-OPC, ie, T 1-3 N2 M0, or T4a-b any N, M0 or any T, N3, M0 or select Stage III ie, T3N1 according to the eighth edition of the AJCC staging manual TNM staging system.
- •Confirmation of acceptable FFPE tumor tissue sample to assess PD-L1 expression.
- •Samples must be acquired less than 3 months prior to first dose of cCRT.
- •For participants with OPC only: documented HPV status by IHC analysis with CINtec® Histology p16 Assay.
- •If not available, a tumor tissue sample should be collected for testing at the central laboratory.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Screening Part I ICF and Screening Part II ICF.
- •Provision of signed and dated written Screening Part I ICF prior to any mandatory study-specific procedures and analyses is required.
排除标准
- •Exclusion criteria Exclusion Criteria should be assessed at Screening Part II only.
- •Participants are excluded from the study if any of the following criteria apply Medical Conditions
- •Histologically, cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the Inclusion Criteria including participants with squamous cell carcinoma of unknown primary or non- squamous histologies eg, nasopharynx or salivary gland.
- •Participants with 1 primary tumors are not eligible for the study.
- •Participants with any of the following: a.Residual disease that needs further treatment with curative intent eg, salvage surgery, neck dissection, and RT after definitive cCRT administration per investigators’ assessment and institutional clinical practice; b.
- •LA-HNSCC that was resected before definitive cCRT c.
- •LA-HNSCC that was treated and is recurrent at the time of screening.
- •Participants who have received RT alone as definitive local therapy for LA HNSCC.
- •T1N0M0 or T2N0M0 HNSCC resected 2 years before the first dose of study intervention with no RT or CTx. b.
- •Malignancy treated with curative intent with no known active disease 2 years before the first dose of study intervention and of low potential risk for recurrence.
结局指标
主要结局
To demonstrate the superiority of volrustomig administered after cCRT relative to observation by assessment of PFS in participants with unresected LA HNSCC with tumors with PD L1 CPS less than equal to 1
时间窗: PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause in the absence of progression. The analysis will include all randomized participants with PD L1 CPS 1 as randomized. All events will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 progression.
Radiological Assessments will be done per RECIST 1.1 Every 12 weeks (± 1 week) from date of randomization up to and including Week 108, then every 16 weeks up to and including Week 204, then every 24 weeks until RECIST 1.1-defined radiological PD
时间窗: PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause in the absence of progression. The analysis will include all randomized participants with PD L1 CPS 1 as randomized. All events will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 progression.
次要结局
- To demonstrate the superiority of volrustomig administered after cCRT relative to observation by assessment of PFS in the unresected LA HNSCC ITT population.(PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause in the absence of progression.The analysis will include all randomized participants. All events will be included regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or clinically progresses prior to RECIST 1.1 progression.)
- To compare and characterize the efficacy of volrustomig administered after cCRT relative to observation by assessment of PFS.(PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause in the absence of progression. These analyses will include participants with CPS 1 as randomized and all randomized participants. The measures of interest are the landmark PFS rates at 12, 24, 36, 48, and 60 months.)
- To compare the efficacy of volrustomig administered after cCRT relative to observation by assessment of OS in participants with unresected LA-HNSCC with tumors with PD L1 CPS 1.(OS is defined as the time from randomization until the date of death due to any cause.)
- To compare and characterize the efficacy of volrustomig administered after cCRT relative to observation by assessment of OS.(OS is defined as the time from randomization until the date of death due to any cause.)
- To compare the efficacy of volrustomig administered after cCRT relative to observation by assessment of OS in the unresected LA-HNSCC ITT population.(OS is defined as the time from randomization until the date of death due to any cause.)
- To compare the efficacy of volrustomig administered after cCRT relative to observation by assessment of PFS2.(PFS2 in participants with PD L1 CPS 1 as randomized and in all randomized participants.)
- To assess the PK of volrustomig.(Concentration of volrustomig in serum and PK parameters such as peak and trough concentrations, as data allow sparse sampling.)
- To investigate the immunogenicity of volrustomig.(Radiological Assessments will be done per RECIST 1.1 Every 12 weeks (± 1 week) from date of randomization up to & including Week 108, then every 16 weeks up to & including Week 204, then every 24 weeks until RECIST 1.1-defined radiological PD)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd.