CTRI/2024/05/067983 [Registered on: 28/05/2024] Trial Registered Prospectively
Last Modified On:
30/03/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
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
Scientific Title of Study
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
Trial Acronym
eVOLVE HNSCC
Secondary IDs if Any
Secondary ID
Identifier
D798EC00001 V1.0 Dated 08 Aug 2023
Protocol Number
NCT06129864
EudraCT
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring, India.
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Details of Contact Person Scientific Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring, India.
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring, India.
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB (Study Sponsor company)
151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Sodertalje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Countries of Recruitment
Republic of Korea Austria Belgium Brazil Canada China Denmark France Germany Hungary India Italy Japan Malaysia Poland Spain Taiwan Thailand Turkey United Kingdom United States of America Viet Nam
Department of Medical Oncology
Kuttisahib Road Cheranelloor, South Chittoor, Kochi, Kerala 682027 Ernakulam KERALA
9400515000
drarun.warrier@astrahospital.com
Dr Deepak Koppaka
Care Hospitals
Department of Medical Oncology
Old Mumbai Highway, Near Cyberabad Police Commissionerate, Jayabheri Pine Valley, HITEC City, Hyderabad, Telangana - 500032 Hyderabad TELANGANA
9052289998
drdeepak.koppaka@gmail.com
Dr Srinivasa B J
HCG Cancer Hospital
Department of Medical Oncology
HCG Tower, No. 8, P Kalinga Rao Road, Sampangi Rama Nagar,
Bengaluru 560 027, Karnataka, India Bangalore KARNATAKA
8033466161
sripav77@gmail.com
Dr Vijay Palwe
HCG Manavata Cancer Centre
Department of Medical Oncology
Manavata Health Campus,Nashik-422002, Maharashtra, India Nashik MAHARASHTRA
97300733733
drpalwe@mcrinasik.com
Dr Ankit Jain
Indraprastha Apollo Hospitals
Department of Medical Oncology
Sarita Vihar, Delhi-Mathura Road, New Delhi-110076, India New Delhi DELHI
7428106406
drankit_j@apollohospitals.com
Dr Santhosh Vandanasetti
Kailash Cancer Hospital & Research Centre
Department of Medical Oncology
Muni Seva Ashram Goraj, Waghodia, Gujarat 391760 Vadodara GUJARAT
9427423693
vandanasetti.santhosh@greenashram.org
Dr Vijay Kumar
King George Medical College
Department of Medical Oncology
Shah Mina Rd, Chowk, Lucknow, Uttar Pradesh 226003 Lucknow UTTAR PRADESH
9935383666
drvkumar2007@gmail.com
Dr Akhil Kapoor
Mahamana Pandit Madan Mohan Malviya Cancer Centre
Department of Medical Oncology
Banaras Hindu University, Campus, Sundar Bagiya Colony, Sundarpur, Varanasi, Uttar Pradesh 221005 Varanasi UTTAR PRADESH
9950482121
kapoorakhil1987@gmail.com
Dr Lalit Mohan Sharma
Mahatma Gandhi Medical College & Hospital
Department of Medical Oncology
Tonk Rd, Ricco Industrial Area, RIICO Institutional Area, Sitapura, Jaipur, Rajasthan 302022 Jaipur RAJASTHAN
9928602244
drlalit2003@gmail.com
Dr Sachin Gupta
Max Super Speciality Hospital (A Unit of Hometrail BuildTech Pvt. Ltd)
Department of Medical Oncology
Near Civil Hospital, Chandigarh Road, Phase 6, Mohali, Punjab, 160055, India Rupnagar PUNJAB
8968839911
Sachin.Gupta@maxhealthcare.com
Dr Kirushna Kumar KS
Meenakshi Mission Hospital and Research Centre
Department of Medical Oncology
Lake Area, Melur Main Rd, Madurai, Tamil Nadu 625107 Madurai TAMIL NADU
9842113003
drkskk@yahoo.com
Dr Chandrakanth MV
NH Rabindranath Tagore International Institute Of Cardiac Sciences
Department of Medical Oncology
Premises No: 1489, Mukundapur Main Road, 124, Eastern Metropolitan Bypass, Mukundapur, Kolkata, West Bengal 700099 Kolkata WEST BENGAL
7003206633
drmvch@gmail.com
Dr Vikas Talreja
Regency Hospital Ltd
Department of Medical Oncology
Tower-2 Day Care 1st floor Regency Hospital Ltd. Sarvodaya nagar Kanpur 208005( U.P) Kanpur Nagar UTTAR PRADESH
9769890961
vikasttalreja@gmail.com
Dr Rejnish Kumar R
Regional Cancer Centre
Department of Medical Oncology
Medical College Kumarapuram Rd, Medical College Campus, Chalakkuzhi, Thiruvananthapuram, Kerala 695011 Thiruvananthapuram KERALA
Volrustomig 750 mg IV infusion Q3W on
Day 1 of each 21-day cycle.
Comparator Agent
Observation Arm
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
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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.
1. Participant must be 18 years of age, at the time of signing the ICF.
2. Histologically or cytologically documented LA squamous cell carcinoma of the OP, HP, OC, or LX with no evidence of M0.
3. 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.
4. 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. If such a sample is not available, a fresh tumor biopsy is required.
5. 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.
6. 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. Before entering Screening Part II, a separate signed and dated written ICF is required. Participants may enter Screening Part II even if the results of the Screening Part I procedures are still pending. If investigators have confirmation of tumor tissue sample availability per tissue sample requirements in Inclusion Criteria 4 and 5, Screening Part I and II ICFs may be signed at the same visit.
Screening Part II
Participants may enter Screening Part II even if the results of the Screening Part I procedures are still pending. Participants are eligible to be randomized to the study only if all of the following Screening Part II inclusion criteria and none of the exclusion criteria apply:
Type of Participant and Disease Characteristics
7. Participants will have completed standard-of-care definitive cCRT with curative intent within 12 weeks 84 days prior to randomization as presented below. If baseline CT, MRI images are equivocal and or residual disease is suspected, investigators are strongly recommended to perform an FDG, PET assessment to confirm absence of progression. Where FDG, PET, avid lesions are detected and accessible, an endoscopy is recommended to be performed and a biopsy taken as clinically indicated to confirm residual disease and evaluate whether participation in this study is appropriate.
a. If cisplatin-based systemic anticancer treatment was administered, participants will have received a cumulative cisplatin dose of 200 mg m2 overall. For example:
High-dose cisplatin for 3 cycles plus concomitant RT
OR
Weekly cisplatin for 6 to 7 cycles plus concomitant RT.
b. If non-cisplatin-based systemic anticancer treatment was administered, participants will have received either:
Carboplatin combined with 5-FU for 3 cycles, plus concomitant RT
OR
Carboplatin combined with paclitaxel for 6 to 7 cycles, plus concomitant RT.
c. In case of toxicity, participants who are not able to receive the last planned systemic anticancer therapy dose as clinically contraindicated, may be eligible provided that all other inclusion criteria and none of the exclusion criteria are met.
d. All participants will have received overall 70 Gy 10 percent of radiation over.
approximately 7 weeks eg, 35 fractions; 1 fraction per day, 5 fractions per week as part of the cCRT regimen per local standard clinical practice. Intensity-modulated radiation therapy technique is highly recommended.
e. Induction CTx prior to cCRT is acceptable if administered per local standard clinical practice.
8. Participants must not have progressed following definitive cCRT therapy with curative intent. Absence of recurrence and/or progression will be assessed by the following imaging procedures up to 12 weeks after the last dose of cCRT.
a. Local disease primary tumor site and neck will be assessed by CT preferred or MRI with contrast from mid-orbits to thoracic inlet.
b. Absence of disease outside of the head and neck will be assessed by CT with contrast preferred of the chest, abdomen including liver, and pelvis as clinically indicated or by MRI if CT with IV contrast is contraindicated.
It is strongly recommended to schedule the baseline imaging assessment after completion of cCRT as close as possible to the planned randomization date.
Participants with residual disease are eligible to this study only if not amenable to other available therapies after definitive cCRT.
If baseline CT, MRI images are equivocal and or residual disease is suspected, investigators are strongly recommended to perform an FDG PET assessment to confirm absence of progression. Where FDG PET-avid lesions are detected and accessible, an endoscopy is recommended to be performed and a biopsy taken as clinically indicated to confirm residual disease and evaluate whether participation in this study is appropriate.
9. Confirmation of PD L1 expression from tumor tissue sample per Inclusion Criterion 4 all participants by the central laboratory. Participants with unknown PD L1 expression prior to randomization are not eligible for the study.
10. For participants with OPC only: confirmation of HPV status by CINtec® Histology p16 Assay. If local test result is not available, then submission of tumor tissue sample per Inclusion Criterion 5 if applicable for HPV status testing at the central laboratory. Participants with unknown HPV status if OPC prior to randomization are not eligible for the study.
11. World Health Organization Eastern Cooperative Oncology Group PS of 0 or 1 with no deterioration that is, WHO ECOG PS 1 over the previous 2 weeks prior to baseline at Screening Part II and prior to randomization.
12. Adequate organ and bone marrow function in the absence of transfusions or growth factor support within 14 days prior to Screening Part II as defined in Table 9
13. Life expectancy 12 weeks.
Weight
14. Body weight 35 kg at screening and at randomization.
Sex and Contraceptive Barrier Requirements
15. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
ExclusionCriteria
Details
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
1. 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.
2. 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.
3. Participants who have received RT alone as definitive local therapy for LA HNSCC.
4. History of another primary malignancy except for
a. 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.
c. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
d. Adequately treated carcinoma in situ without evidence of disease.
e. Cancer participant with incidental histologic findings of prostate cancer that,in the opinion of the investigator, is not deemed to require active therapy eg, incidentalprostate cancer identified following cystoprostatectomy that is TNM Stage pT2N0 may be enrolled.
5. Unresolved toxicities caused by previous anticancer therapy, defined as toxicities other than alopecia and vitiligo not yet resolved to NCI CTCAE Version 5.0 Grade 1 or baseline. Participants with an irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included.eg, hearing loss.
6. As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.
7. Evidence of the following infections:
a. Active infection including TB clinical evaluation that includes clinical history, physical examination, and radiographic findings and TB testing in line with local standard clinical practice.
OR
b. Uncontrolled HIV infection, the following criteria are required to define well-controlled HIV infection.
Undetectable viral RNA load for 6 months,
Cluster of differentiation 4 count of 500 cells μL, stable for at least 6 months on the same anti-HIV medications, and
No history of AIDS (defined by either CD4 T cell count 200 cells μL and or AIDS-defining opportunistic infection.
OR
c Active or uncontrolled HBV or HCV. Participants are eligible if they:
Have controlled HCV viral load defined as undetectable HCV RNA by polymerase chain reaction either spontaneously or in response to a successful prior course of anti-HCV therapy.
Have received HBV vaccination with only anti-hepatitis B surface antibody positivity and no clinical signs of HBV.
Are hepatitis B surface antigen HBsAg and anti-hepatitis B core antibody HBc ie, those who have cleared HBV after infection and meet all conditions
below:
o Are HBsAg+ with chronic HBV infection lasting 6 months or longer and meet all conditions below:
HBV DNA viral load 100 IU mL.
Have normal transaminase values.
Start or maintain antiviral treatment if clinically indicated as per investigator judgment.
OR
d Active hepatitis A.
8. As judged by the investigator, any evidence of diseases such as severe or uncontrolled systemic diseases, including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure [as defined by New York Heart Association Class 2, uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction within the past 12 months, ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness social situations that would limit compliance with study requirements, substantially increased risk of incurring AEs or compromise the ability of the participant to give written informed consent, and active bleeding diseases and or history of organ transplant or allogenic stem cell transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
9. Active or prior documented autoimmune or inflammatory disorders including
inflammatory bowel disease eg, colitis or Crohn’s disease, diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonitis past medical history of ILD, drug induced ILD, or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD, etc. The following are exceptions to this criterion:
a. Participants with vitiligo or alopecia.
b. Participants with hypothyroidism eg, following Hashimoto syndrome stable on HRT.
c. Any chronic skin condition that does not require systemic therapy.
d.Participants without active disease in the last 5 years prior to enrollment may be included but only after consultation with the Study Clinical Lead.
e. Participants with celiac disease controlled by diet alone.
10. Participant meets one or more of the following:
a.History of QT prolongation associated with other medications that required discontinuation of that medication.
b.Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
c.History of arrhythmia multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, which is symptomatic or requires treatment CTCAE Grade 3, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgment with cardiologist consultation recommended.
11. Untreated or progressive central nervous system metastatic disease, any leptomeningeal disease, or cord compression.
Prior, Concomitant Therapy
12. Any concomitant medication known to be associated with Torsades de Pointes.
13. Receipt of the last dose of anticancer therapy CTx and or RT12 weeks 84 days prior to randomization.
14. Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded.
15. Any concurrent CTx, RT, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions eg, insulin for diabetes and HRT is acceptable. Note, Local treatment for palliative procedures to address obstruction, compression, pain or bleeding is acceptable, as long as disease recurrence or progression is unequivocally ruled out.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
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
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
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.
Secondary Outcome
Outcome
TimePoints
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.
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 or receives another anticancer therapy.
The measure of interest is the HR of OS.
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.
These analyses will include participants with CPS 1 as randomized and all randomized participants.
The measures of interest are the landmark OS 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 the unresected LA-HNSCC ITT population.
OS is defined as the time from randomization until the date of death due to any cause.
The analysis will include all randomized participants. All events will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
The measure of interest is the HR of OS.
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.
PFS2 is defined as the time from randomization until the earliest of the progression event following the initial investigator assessed progression, after the start of the first subsequent therapy, or death from any cause, whichever occurs first. The date of the second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice.
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
Safety & Tolerability will be assessed via Vital, Signs, Hematology, Clinical Biochemistry, physical Examination: Will be assessed at Baseline, C1D1, C1D8, C1D15, C2D1, C2D8, C2D15, C3-C18 (CXD1)
Target Sample Size
Total Sample Size="1140" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
is a Phase III, 2-arm, randomized, open-label, multi-center, global studyassessing the efficacy and safety of
volrustomig compared to observation in participants with unresected LA-HNSCC(tumor sitesinclude: HPV-positiveOP,
HPV-negativeOP, OC, HP,andLX)
Stage III to IVA/B whose disease has not progressed following the completion of
definitive cCRT.
Approximately1590participantswithLA-HNSCCareplannedtobescreened inorderto randomize
approximately 1145 participants in a 1:1 ratio to one ofthe following arms:
Day1 ofeach21-daycycleforupto12monthsor18cycles, or untilRECIST
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.
·ArmB- Observation:Participantsintheobservationarmwillundergoobservationforup 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 willbe observed during this study.
Randomization
will be stratified according to PD-L1 expression (CPS < 1 versus CPS 1 to 19versusCPS≥20),primarytumorsite/HPVstatus(HPV-positiveOPversusHPV-negative OP versus OC/HP/LX), CTxutilizedin definitive cCRT (cisplatin-based versus others), and tumor and nodalstage (< T4 and < N2c [or < N3 if
HPV-positive OPC] versus T4 and/or
≥N2c[orN3ifHPV-positiveOPC]).
Recruitment
ofparticipantswithexpressionofPD-L1CPS<1willbecappedat amaximum
of 20% of the total randomized participants (ie, 229 participants), so that
approximately
916participantswithPD-L1CPS≥1will
berandomized.Recruitment ofparticipantswith LX
tumor subtype willbe 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
undergoobservationfor12months,oruntilRECIST1.1‑definedradiologicalPD confirmed byinvestigatorassessment,unlessthereisevidenceofunacceptabletoxicity,orifaparticipant requests
to stop the study intervention, as applicable to the arm participants are
assigned to.
Participants
who discontinue studyintervention
for reasons other than RECIST 1.1-defined radiological PD must have
post-treatment follow-up tumor assessments as per the protocoluntilRECIST1.1-definedradiologicalPDasassessedbyinvestigator assessment, or
other study discontinuation criterion per protocol.
For
participants withOPC only,
documented HPV status byIHC analysis
with CINtec® Histologyp16Assay.Ifnotavailableatthetimeofscreening,atumor
sampleshouldbe collected for testing at the central laboratory.
If
study intervention or observation is permanently discontinued, the participant
should, if possible,remaininthestudy.Notethatdiscontinuationfromstudyinterventionorobservation is not the same thing as a discontinuation
or withdrawal from the study
After
study intervention discontinuation, participants will undergo an end oftreatment visit (30 days post last dose
[± 7 days]) and will be followed up for safety assessments 90 days (±7days)aftertheirlastdoseofstudyintervention(ie,thesafetyfollow-upvisit). Additional
assessments to be performed at the time of the 90-daysafety follow-up visit are detailed in the protocol SoA.
ParticipantswhohavediscontinuedstudyinterventionintheabsenceofRECIST1.1-defined radiological PD by
investigator assessment will be followed up with tumor assessments accordingtothe protocol SoAuntilRECIST1.1-definedPDordeath,regardlessofwhether
ornottheparticipantstartedasubsequentanticancertherapy,unlesstheyhavewithdrawnall consent to study-related assessments.
ParticipantswillbefollowedupforsurvivalstatusafterPDevery12weeks(±7days)until death, withdrawal of consent, or the end of the study (ie,
progression/survival follow-up).
Survivalinformationmaybeobtainedviatelephonecontactwiththeparticipantorthe participant’s
family, or by contact with the participant’s current physician.
Participantswillbefollowedupforsurvivalstatusevery12weeks(±7days)afterthesafety
follow-up visit, as indicated in the protocol SoAs until death, withdrawal of consent,
lost to follow-up, or the end of the study. Survivalinformation may be obtained via telephone contact with the
participant or the participant’s family, or bycontact 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.