CTRI/2025/04/084960 [Registered on: 16/04/2025] Trial Registered Prospectively
Last Modified On:
14/04/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Metastatic Squamous NSCLC Whose Tumors Express PD-L1
Scientific Title of Study
A Phase III, Randomized, Double-blind, Multicenter, Global Study of Rilvegostomig or Pembrolizumab in Combination with Platinum-based Chemotherapy for the First-line Treatment of Patients with Metastatic Squamous Non-small Cell Lung Cancer Whose Tumors Express PD-L1 (ARTEMIDE-Lung02)
Trial Acronym
ARTEMIDE-Lung02
Secondary IDs if Any
Secondary ID
Identifier
CT/24/000131
ClinicalTrials.gov
D702BC00001 Version 2.0 date 06 Aug 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Oncology 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, Oncology 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, Oncology 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
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
Argentina Australia Belgium Belize Canada China France Germany Hungary India Israel Italy Japan Malaysia Netherlands Peru Poland Republic of Korea Spain Taiwan Thailand Turkey United Kingdom United States of America Viet Nam Austria
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Parveen Jain
Aakash Healthcare Super Speciality Hospital
Department of oncology
Hospital Plot Road Number 201, Dwarka Sector 3, New Delhi – 110075
New Delhi DELHI
9811775324
drparveen1010@gmail.com
DrSachin Khurana
All India Institute of Medical Sciences
Department of oncology
Sri Aurbindo Marg Ansari Nagar Ansari Nagar East Delhi 110029 New Delhi DELHI
9769030180
dr.sachinkhurana@gmail.com
Dr Bivas Biswas
Apollo Multispecialty Hospitals Limited
Department of oncology
58, Canal Circular Road, Kolkata – 70005
Kolkata WEST BENGAL
9830933005
bivasbiswas@gmail.com
Dr Kaushal Patel
First Cure Hospital
Department of oncology
VIP Galleria, Above Dhiraj Sons/ Alpha Bazar, Althan, Surat - 395017
Surat GUJARAT
9723431102
kpatel291980@gmail.com
Dr Mukesh Chaudhari
HCG Manavata Cancer Center
Department of oncology
Behind Shivang Auto, Mumbai Naka, Nashik – 422002
Nashik MAHARASHTRA
9096920416
drmukesh@mcrinasik.com
Dr Shuvadeep Ganguly
Jawaharlal Institute of Postgraduate Medical Education Research (JIPMER)
Department of oncology
Jimper Campus Road, Gorimedu Dhanvanthari Nagar, 3rd floor, JIPMER, Super speciality Building, Pondicherry – 605006
Pondicherry PONDICHERRY
9654215495
ganguly.shuvadeep@gmail.com
Dr Bipinesh Sansar
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Department of oncology
Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus, Varanasi – 221005 Varanasi UTTAR PRADESH
8002583913
bipinesh04@yahoo.co.in
Dr Krishna Kumar Ratnam
Meenakshi Mission Hospital & Research Centre
Department of oncology
Lake Area, Melur Road, Madurai, Tamil Nadu – 625107
Madurai TAMIL NADU
9380417299
kkrathnam@gmail.com
Dr Prashanth P
MVR Cancer Centre and Research Institute
Department of oncology
CP13/516 B C Vellalasseri NIT (Via) Poolacode Kozhikode Kerala 673601
Kozhikode
KERALA Kozhikode KERALA
9847141122
drprasanth@mvrccri.co
Dr Nandini Menon
Tata Memorial Centre
Department of oncology
R. No. 1109, 11th Floor, Homi Bhabha Block, Dr Ernest Borges Marg Parel, Mumbai- 400012
Mumbai MAHARASHTRA
9769178270
nandini.menon1412@gmail.com
Details of Ethics Committee
No of Ethics Committees= 10
Name of Committee
Approval Status
Aakash Healthcare Institutional Ethics Committee
Submittted/Under Review
IEC Intervention Studies JIPMER
Submittted/Under Review
Institute Ethics Committee, All India Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee Apollo Multispecialty
Approved
Institutional Ethics Committee MPMMCC
Submittted/Under Review
Institutional Ethics Committee MVR
Submittted/Under Review
Institutional Ethics Committee of MMCH and RI
Approved
Manavata Clinical Research Institute Ethics Committee
Submittted/Under Review
TMH Institutional EC, TMH
Submittted/Under Review
VMH Institutional Ethics Committee First Cure Hospital
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Control Arm
Pembrolizumab
pembrolizumab 200 mg iv Q3W in combination with carboplatin
AUC 6 iv Q3W and paclitaxel 200 mg/m2 iv Q3W or nab-paclitaxel 100 mg/m2 iv Day 1,
8, and 15 of each 3-week cycle for 4 cycles followed by pembrolizumab 200 mg iv Q3W.
Intervention
Experimental Arm
Rilvegostomig
rilvegostomig 750 mg iv Q3W in combination with
carboplatin AUC 6 iv Q3W and paclitaxel 200 mg/m2 iv Q3W or nab-paclitaxel
100 mg/m2 iv Day 1, 8, and 15 of each 3-week cycle for 4 cycles followed by
rilvegostomig 750 mg iv Q3W.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply
1. Participant must be greater than or equal 18 at the time of signing the ICF.
2.Histologically or cytologically documented squamous NSCLC.
3.Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
4.Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any actionable driver oncogenes for which there are locally approved targeted 1L therapies.
5.WHO/ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization.
6.Minimum life expectancy of 12 weeks.
7.Provision of acceptable tumor sample, as defined in the Pathology Manual and Laboratory Manual and summarized in Section 8.8, to confirm tumor PD-L1 expression TC greater than or equal 1% using the VENTANA PD-L1 (SP263) Assay at a Sponsor-designated central laboratory prior to randomization. Participants with unknown PD-L1 status or TC lesser than1% are not eligible for the study.
8.At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as greater than or equal 10 mm in the longest diameter (except lymph nodes, which must have short axis greater than or equal 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
9. Adequate organ and bone marrow function as defined in below table.
10. Minimum body weight of 30 kg.
11. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
12. Female participants of childbearing potential:
(a) Must have negative pregnancy test at screening and prior to each Day 1
administration of study intervention.
(b) If sexually active with a non-sterilized male partner, must use at least 1 highly
effective method of birth control from screening to 4 months after the last dose of
blinded study treatment and 6 months after last dose of chemotherapy.
(c) Non-sterilized male partners of female participants of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
(d) Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy.
13. Non-sterilized male participants who are sexually active with a female partner of childbearing potential:
(a) Non-sterilized male participants who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
(b) Female partners (of childbearing potential) of a male participant also must use at least 1 highly effective method of contraception throughout their participation in the study, and until at least 4 months after their male partners last dose of blinded study treatment and 6 months after last dose of chemotherapy.
(c) Male participants must refrain from fathering a child or donating sperm during the study and for 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy.
14. Capable of giving signed informed consent as described in Appendix A of the CSP which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
15. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative
16. All races, gender, and ethnic groups are eligible for this study
ExclusionCriteria
Details
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply
Medical Conditions
1. As judged by the investigator, any severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; ILD (of any grade), serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease), active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment, psychiatric illness/social situations, substance abuse, or significant cardiac conditions 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.
2. History of organ transplant.
3. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
4. History of another primary malignancy except for malignancy treated with curative intent with no known active disease greater than or equal 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
5. Presence of small cell and neuroendocrine histology components.
6. Persistent toxicities (CTCAE Grade greater than or equal 2) caused by previous anticancer therapy, excluding alopecia. Participants may be enrolled with the following chronic
stable Grade 2 toxicities (defined as no worsening to greater than Grade 2 for at least 3 months prior to the first dose of study intervention and managed with SoC treatment) which the investigator deems related to previous anticancer therapy:
(a) Chemotherapy-induced neuropathy.
(b) Fatigue.
(c) Vitiligo.
(d) Endocrine disorders, that are controlled with replacement hormone therapy.
(e) Participants with 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).
7. Spinal cord compression.
8. Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrollment. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure).
9. Active primary immunodeficiency/active infectious disease(s)
Known active hepatitis A, chronic or active hepatitis B, or chronic or active hepatitis C infection
Participants who have chronic HBV and are receiving suppressive antiviral therapy are allowed to be enrolled if viral load is controlled and ALT is normal. Those with ALT lesser than 3 × ULN (in presence of liver metastases), not attributable to HBV infection and with controlled viral load could be enrolled. Controlled hepatitis B viral load is defined as serum HBV DNA lesser than 100 U/mL by PCR. Participants with controlled hepatitis B viral load must remain on antiviral therapy, per institutional practice, during the study treatment and follow-up period to ensure adequate viral suppression.
Participants who have chronic HCV are allowed to be enrolled if ALT is normal and HCV RNA undetectable by PCR, either spontaneously or in response to a successful prior course of anti-hepatitis C therapy (Regev et al 2020). Controlled hepatitis C viral load is defined as undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy
Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4pluse count of greater then 350 cell, no history of AIDS defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti HIV medications.
10. Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice)
11. History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure (as defined by New York Heart Association
class greater than or equal 3), history of myocardial infarction within the past 6 months.
12. Medical contraindication to platinum-based doublet chemotherapy.
Prior/Concomitant Therapy
13. Any concomitant medication known to be associated with Torsades de pointes.
14. Any prior systemic therapy received for advanced or mNSCLC.
Note: Prior systemic therapy in the neoadjuvant or adjuvant setting and/or definitive radio- or chemoradiotherapy for early-stage resectable disease are allowed, provided that recurrence or progression has occurred Grater then12 months after the end of treatment.
15. Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
16. Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
17. Any concurrent chemotherapy, radiotherapy, immunotherapy, investigational, or biologic or hormonal therapy for cancer treatment other than those under investigation in this study. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, insulin for diabetes, HRT, gonadotropin-releasing hormone analogs, and bisphosphonates) is acceptable
18. Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
Note: Local treatment of isolated lesions for palliative intent is acceptable
19. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
Note: Local surgery of isolated lesions for palliative intent is acceptable.
20. Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention is excluded. The following are exceptions to this criterion:
(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection).
(b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication), as premedication for chemotherapy, or a single dose for alliative
purpose (eg, pain control).
(c) Systemic corticosteroids at physiological doses not to exceed 10 mg/day of
prednisone or 2 mg/day of dexamethasone or equivalent (except for the treatment
of adverse events)
21. 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.
22. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
Note: Participants, if enrolled, should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of study intervention.
Prior/Concurrent Clinical Study Experience
23. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 12 months or the combination/comparator agent (unless the safety profile is known prior to randomization), or concurrent enrollment in another clinical study (unless the study is observational [non-interventional], or the participant is in the follow-up period of an interventional study).
24. Participants with a known hypersensitivity to study intervention or any excipients of the products.
Other Exclusions
25. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
26. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
27. Previous enrollment in the present study.
28. For females only: Currently pregnant (confirmed with positive pregnancy test) or breast-feeding, or who are planning to become pregnant.
29. Female participants should refrain from breastfeeding from screening throughout the study and until 4 months after last dose of blinded study treatment and 6 months after last dose of chemotherapy
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS
To demonstrate the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS
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 deaths 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
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).
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 radiographic progression per RECIST 1.1. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits.
The measure of interest is the HR of PFS.
Secondary Outcome
Outcome
TimePoints
To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS
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 deaths will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
The measures of interest are the landmark OS rates at 12, 24, 36, and 48 months
To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS
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).
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 radiographic progression per RECIST 1.1. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits.
The measures of interest are the landmark PFS rates at 12, 24, and 36 months.
To compare the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS2
PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial investigator-assessed progression event), 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.
The analyses will include all randomized participants. All events will be included, regardless of whether the participant withdraws from subsequent therapy and regardless of missed visits.
The measure of interest is the HR of PFS2
To characterize and compare the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of ORR
ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by BICR assessments using RECIST 1.1.
The analyses will include all randomized participants.
Data obtained from randomization up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who discontinue treatment without a response or progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR analysis.
The measure of interest is the difference of the ORR.
To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of DoR
DoR is defined as the time from the date of first documented response until the date of documented progression per BICR assessments using RECIST 1.1 or death due to any cause (in the absence of progression).
The analyses will include all randomized participants who have a confirmed response. The end of response coincides with the date of progression or death from any cause used for the PFS endpoint.
The measure of interest is the median of DoR.
To assess the PK of rilvegostomig
Concentration of rilvegostomig in serum.
To investigate the immunogenicity of rilvegostomig
Presence ADAs, titer, and neutralizing antibodies for rilvegostomig.
To assess patient-reported physical Functioning
Proportion of participants with maintained or improved physical functioning as measured by PROMIS PF-SF 8c – 7 day at each time point.
The analysis will include all randomized participants.
The measure of interest is the proportion of participants with maintained or improved physical functioning at each time point.
To assess patient-reported GHS/QoL
To assess patient-reported lung cancer
symptoms of NSCLC
TTD of GHS/QoL as measured by the EORTC IL172.
TTD is defined as time from randomization to the date of first deterioration.
The analysis will include all randomized participants.
The measure of interest is the HR of TTD of GHS/QoL.
o assess patient-reported lung cancer
symptoms of NSCLC
TTD in pulmonary symptoms as measured by the NSCLCSAQ.
TTD is defined as time from randomization to the date of first deterioration.
The analysis will include all randomized participants.
The measure of interest is the HR of TTD of lung cancer symptoms.
Target Sample Size
Total Sample Size="880" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
05/05/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
18/11/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
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, two-arm, randomized, double-blind, multicenter, global study to assess the efficacy and safety of rilvegostomig in combination with platinum-based chemotherapy compared with pembrolizumab in combination with platinum-based chemotherapy in participants with squamous mNSCLC and whose tumors express PD-L1 (TC greater than or equal 1%).
Approximately 1760 participants will be screened to achieve approximately 880 participants randomized into the study. Participants will be randomized in a 1:1 ratio to one of the following intervention arms:
·Arm A (experimental arm): rilvegostomig 750 mg iv Q3W in combination with carboplatin AUC 6 iv Q3W and paclitaxel 200 mg/m2 iv Q3W or nab-paclitaxel 100 mg/m2 iv Day 1, 8, and 15 of each 3-week cycle for 4 cycles followed by rilvegostomig 750 mg iv Q3W. Use of carboplatin AUC 5 and/or paclitaxel 175mg/m2 is permitted per local practice.
·Arm B (control arm): pembrolizumab 200 mg iv Q3W in combination with carboplatin AUC 6 iv Q3W and paclitaxel 200 mg/m2 iv Q3W or nab-paclitaxel 100 mg/m2 iv Day 1, 8, and 15 of each 3-week cycle for 4 cycles followed by pembrolizumab 200 mg iv Q3W.
·Use of carboplatin AUC 5 and/or paclitaxel 175mg/m2 is permitted per local practice.
Participants will continue to receive study treatment until RECIST 1.1-defined PD (per investigator assessment), unacceptable toxicity, or until any other discontinuation criteria are met.
Randomization will be stratified by PD-L1 expression (TC 1% to 49% versus greater than or equal 50%), choice of chemotherapy (paclitaxel versus nab-paclitaxel) and region (China versus Asia [other] versus rest-of-world). Participants will be prospectively tested for PD-L1 expression for eligibility and stratification. Participants must have a tumor tissue sample available for PD-L1 IHC testing performed by a central reference laboratory during the screening period. PD-L1 status is required prior to randomization. PD-L1 status will be determined by VENTANA PD-L1 (SP263) Assay in the submitted tumor sample.
Participants in both experimental and control arms will receive iv infusion Q3W until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, or until any other intervention discontinuation criterion is met. Following radiological disease progression, participants may continue to receive blinded study treatment until confirmed with a subsequent scan (performed at least 4 weeks later) as long as they continue to show clinical benefit.
Follow-up of Participants Post Discontinuation of Study Intervention:
All participants will be followed up for safety assessments until 90 days ( ±7 days) after their last dose of study intervention. Participants who have discontinued study intervention for reasons other than disease progression will be followed up with tumor assessments as per the SoA.
All participants will be followed up for survival status and time to second progression or death (PFS2) every 12 weeks (±7 days) until death, withdrawal of consent, or the end of the study.