CTRI/2023/05/052218 [Registered on: 02/05/2023] Trial Registered Prospectively
Last Modified On:
24/02/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized Factorial Trial
Public Title of Study
Study of Datopotamab Deruxtecan (Dato-DXd) for first line treatment of patients with locally advanced or metastatic NSCLC
Scientific Title of Study
A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)
Trial Acronym
AVANZAR
Secondary IDs if Any
Secondary ID
Identifier
D926NC00001 V1.0 Date 15 Jul 2022 NCT 05687266
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring
Affiliation
AstraZeneca Pharma India Ltd
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
Email
sandeep.av@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring
Affiliation
AstraZeneca Pharma India Ltd
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road
KARNATAKA 560045 India
Phone
9845079472
Fax
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 Södertälje 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
Australia Brazil Bulgaria Canada China Denmark France Germany Greece Hungary India Italy Japan Mexico Peru Poland Republic of Korea Spain Sweden Taiwan Turkey United Kingdom United States of America Viet Nam
Institutional Ethics Committee - All India Institute of Medical Sciences
Approved
Institutional Ethics Committee - Bhagwan Mahaveer Hospital and Research
Approved
Institutional Ethics Committee -Meenakshi Mission Hospital and Research Centre
Approved
Institutional Ethics Committee Jawaharlal Institute of Postgraduate Medical Education & Research
Approved
Institutional Ethics Committee MVR Cancer Hospital & Research Institute
Approved
Institutional Review Board - Rajiv Gandhi Cancer Institute and Research Centre
Approved
Institutional Review Board Tata Medical Center
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
Intervention
Datopotamab Deruxtecan Durvalumab Carboplatin
Dato DXd 6.0 mg/kg plus durvalumab 1120 mg plus carboplatin AUC 5 mg/mL/minute, i.v. Q3W for 4 cycles.
Maintenance with Dato DXd 6.0 mg/kg plus durvalumab 1120 mg, i.v. Q3W
Histology-specific therapy with either Non-squamous NSCLC: Pembrolizumab 200 mg plus pemetrexed 500 mg/m2 plus either carboplatin AUC 5 mg/mL/minute or cisplatin 75 mg/m2 i.v. Q3W for 4 cycles;
Squamous NSCLC: Pembrolizumab 200 mg plus paclitaxel 200 mg/m2 plus carboplatin (AUC 5 or 6 mg/mL/minute), i.v. Q3W for 4 cycles
Maintenance with:
Pembrolizumab 200 mg (maximum of 35 cycles or 2 years [whichever occurs first]), with or without pemetrexed 500 mg/m2; or
Pembrolizumab 200 mg monotherapy (maximum of 35 cycles or 2 years [whichever occurs first])
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Age
1. Participant must be ≥ 18 years at the time of screening.
Type of Participant and Disease Characteristics
2. Histologically or cytologically documented NSCLC that:
a) Is Stage IIIB or IIIC disease not amenable for surgical resection or definitive chemoradiation, or Stage IV metastatic NSCLC disease at the time of randomisation who have not received prior chemotherapy or other systemic therapy for first-line Stage IIIB, IIIC or IV NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for early stage disease (Stage I to IIIA) are eligible, provided that progression has occurred 6 months from the last dose of checkpoint inhibitor, chemotherapy, or other systemic anti-cancer therapy.
b) Lacks sensitising EGFR tumour tissue mutation (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), as well as ALK and ROS1 rearrangements.
c) Has no documented tumour genomic alteration results in NTRK, BRAF, RET, MET or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies.
Note: Participants whose tumours harbour KRAS mutations are eligible for the study.
3. ECOG PS of 0 or 1 with no deterioration over the previous 2 weeks prior to day of first dosing.
4. FFPE tumour sample collected prior to signing of informed consent, ie, the start of screening.
5. Tumour PD-L1 status defined as TC 1%, TC 1% to 49%, or TC 50%, determined using the VENTANA PD-L1 (SP263) IHC Assay by a central laboratory. Participants with unknown central PD L1 status are not eligible for the study.
6. TROP2 biomarker status as determined retrospectively using the VENTANA TROP2 IHC QCS Assay (clinical trial assay), or prospectively once a TROP2 IHC QCS assay is validated in a CAP/CLIA laboratory. Participants with unknown central TROP2 biomarker status are not eligible for the study once prospective testing is implemented.
7. At least 1 lesion, not previously irradiated, that qualifies as a target lesion (TL) per RECIST 1.1 at baseline and can be accurately measured at baseline as 10 mm in the longest diameter (except lymph nodes, which must have short axis 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
8. Adequate bone marrow reserve and organ function within 7 days before randomisation defined as:
Haemoglobin 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
Absolute neutrophil count 1.5 109/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment).
Platelet count 100 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment).
International normalised ratio/prothrombin time and either partial thromboplastin time or activated partial thromboplastin time 1.5 ULN.
TBL 1.5 ULN or 3 ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
ALT and AST 3 ULN (5 ULN in participants with liver metastases).
Calculated CrCL 40 mL/min as determined by Cockcroft Gault (using actual body weight).
9. Minimum life expectancy of 12 weeks.
Sex
10. Male and/or female.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Reproduction:
11. Negative pregnancy test (serum) for women of childbearing potential who are sexually active with a non-sterilised male partner.
12. Female participants must be 1 year postmenopausal, surgically sterile, or using 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). For women who are on HRT please refer to Appendix G. Women of childbearing potential who are sexually active with a non sterilised male partner must agree to use 1 highly effective method of birth control (see Appendix G for complete list of highly effective birth control methods). They should start their chosen method of birth control during screening and continue to use it throughout the total duration of the drug treatment and the drug washout period
13. Male participants who intend to be sexually active with a female partner of childbearing
potential must be surgically sterile or using an acceptable method of contraception (see
Appendix G) from the time of screening throughout the total duration of the study and the
drug washout period (90 days after the last dose of durvalumab or 180 days after the last
dose of tremelimumab, whichever is longer) to prevent pregnancy in a partner. Male
participants must not donate or bank sperm during this same time period.
Informed Consent
14. Capable of giving signed informed consent as described in Appendix A, which includes
compliance with the requirements and restrictions listed in the ICF and in this protocol
ExclusionCriteria
Details
Exclusion criteria
Medical conditions
1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, active systemic infection (except for HBV infection or HCV infection), active interstitial lung disease (ILD) pneumonitis, serious chronic gastrointestinal conditions associated with diarrhea, psychiatric illness/social situations) or history of allogeneic organ transplant that, 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. Uncontrolled arterial hypertension defined by a systolic pressure 150 mm Hg or diastolic pressure 90 mm Hg or other hypertensive cardiovascular complications despite standard medical management.
3. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of Lenvatinib.
4. History of another primary malignancy. Exceptions include: 1) malignancy treated with curative intent or has low potential risk for recurrence with no known active disease 5 years before the first dose of study intervention; 2) malignancy which occurred 5 years before the first dose of study intervention, is not active, and not expected to recur or be clinically relevant in the next 5 years (may be considered pending further to discussion with the study physician prior to randomization).
5. Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE]
Grade 2) caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included (eg, hearing loss) after consultation with the AstraZeneca study clinical lead.
6. 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, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis and autoimmune myocarditis). The following are exceptions to this criterion:
Participants with vitiligo or alopecia.
Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
Any chronic skin condition that does not require systemic therapy
Participants without active disease in the last 5 years may be included but only after consultation with the study clinical lead.
Participants with coeliac disease controlled by diet alone.
7. History of leptomeningeal carcinomatosis.
8. Co-infection with HBV and hepatitis D virus (HDV). (The HBV infection is indicated by the presence of HBsAg and/or anti-HBcAb with detectable HBV DNA 10 IU/mL or above the limit of detection per local lab standard; HDV positive infection is indicated by the presence of anti-HDV antibodies.)
9. Known to have tested positive for human immunodeficiency virus (HIV) (positive
HIV 1/2 antibodies) or tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
10. History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac 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 upon discussion with the study clinical lead.
11. Any history of nephrotic or nephritic syndrome.
12. Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC, or mixed cholangiocarcinoma and HCC.
13. History of hepatic encephalopathy or porto-systemic shunt within past 12 months or
requirement for medications to prevent or control encephalopathy (ie, no lactulose,
rifaximin, etc, if used for purposes of hepatic encephalopathy).
14. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
• Participants with ascites that has required pharmacologic intervention (eg, diuretics) and who have been on stable doses of diuretics for ascites for 2 months are eligible.
15. Major portal vein thrombosis visible on baseline/eligibility imaging. Participants with
Grade Vp3 and Vp4 are excluded.
16. Evidence by investigator assessment of varices at risk of bleeding on upper endoscopy undertaken at the screening visit, or within 6 months (24 weeks) of randomization.
Prior/Concomitant Therapy
17. Receipt of prior systemic anticancer therapies for HCC.
18. Receipt of more than 1 prior embolization treatment/procedure with palliative intent
(embolization procedures as part of curative therapy are not restricted). Prior radiotherapy (eg, transarterial radioembolization [TARE], SBRT) is permitted if > 6 months prior to randomization.
19. Prior exposure to immune-mediated therapy including, but not limited to, other
antiCTLA-4, anti-PD-1, anti-PD-L1, antiPD-L2, and anti-VEGF antibodies, excluding
therapeutic anticancer vaccines.
20. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab, tremelimumab, or lenvatinib. The following are exceptions to this
criterion:
• Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
• Steroids as premedication for hypersensitivity reactions or as an anti-emetic (eg, CT scan premedication).
21. Receipt of live attenuated vaccine within 30 days prior to the first dose of study
intervention .
22. Major surgical procedure or significant traumatic injury within 4 weeks of the first dose
of study intervention or an anticipated need for major surgery during the study. Biopsy
from any type of surgery within 28 days is not an exclusion criteria nor are procedures to treat varices.
Prior/Concurrent Clinical Study Experience
23. Previous randomization in the present study or a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
24. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
25. Participants with a known hypersensitivity to durvalumab, tremelimumab, and/or
lenvatinib or any of the excipients of the products.
Other Exclusions:
26. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
27. 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.
28. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of tremelimumab, whichever is longer.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of PFS by BICR in first line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of OS in first-line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC
PFS using BICR assessments according to RECIST 1.1 will be assessed at Baseline followed by every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1 defined radiological PD plus an additional follow-up scan at least 4 weeks later
Secondary Outcome
Outcome
TimePoints
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of PFS by BICR in first line treatment of participants with locally advanced or metastatic NSCLC (ITT population)
PFS using BICR assessments according to RECIST 1.1 will be assessed at Baseline followed by every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1 defined radiological PD plus an additional follow-up scan at least 4 weeks later
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of OS in first-line treatment of participants with locally advanced or metastatic NSCLC (ITT population)
Assessments for survival after intervention discontinuation will be conducted every 3 months (± 7 days) until death, withdrawal of consent or the end of study
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of PFS by BICR in first line treatment of TROP2 biomarker negative participants with locally advanced or metastatic NSCLC
PFS using BICR assessments according to RECIST 1.1 will be assessed at Baseline followed by every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1 defined radiological PD plus an additional follow-up scan at least 4 weeks later
To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of OS in first-line treatment of TROP2 biomarker negative participants with locally advanced or metastatic NSCLC
Assessments for survival after intervention discontinuation will be conducted every 3 months (± 7 days) until death, withdrawal of consent or the end of study
To demonstrate the effectiveness of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of ORR in first-line treatment of participants with locally advanced or metastatic NSCLC
Evaluation of CR or PR as determined by BICR and investigator per RECIST 1.1 assessed at Baseline, every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation
To demonstrate the effectiveness of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of DoR in first line treatment of participants with locally advanced or metastatic NSCLC
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator assessment or death due to any cause. This will be based on the radiology assessments performed at Baseline and then every 6 weeks up to Week 12, then every 9 weeks up to Week 48 and then every 12 weeks thereafter
To demonstrate the effectiveness of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy by assessment of PFS in first line treatment of participants with locally advanced or metastatic NSCLC by investigator’s assessment
PFS using Investigator’s assessments according to RECIST 1.1 will be assessed at Baseline followed by every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1 defined radiological PD plus an additional follow-up scan at least 4 weeks later
To assess participant-reported pulmonary symptoms of NSCLC in participants treated with Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy
TTD in pulmonary symptoms (dyspnoea, cough and chest pain) as measured by the NSCLC-SAQ at Baseline and Every 3 weeks from C1 Day 1 for the first 51 weeks and every 6 weeks thereafter until EoT, at EoT, and then every 6 weeks (relative to C1 Day 1) after EoT until 18 weeks after PD
To assess participant-reported physical functioning in participants treated with Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum based chemotherapy
Time to Deterioration in physical functioning as measured by PROMIS Physical Function short form 8c at Baseline and Every 3 weeks from C1 Day 1 for the first 51 weeks and every 6 weeks thereafter until EoT, at EoT, and then every 6 weeks (relative to C1 Day 1) after EoT until 18 weeks after PD
To assess the PK of Dato-DXd when combined with durvalumab and carboplatin
Concentration of Dato-DXd, total anti TROP2 antibody, and MAAA 1181a (payload deruxtecan) in plasma and PK parameters collected at C1D1 followed by C4D1 and C8D1
To investigate the immunogenicity of Dato DXd when combined with durvalumab and carboplatin
Presence of Antidrug Antibody for Dato-DXd. Samples will be collected from patient randomized on Dato-Dxd arm. Pre-dose at Cycles 1, 2, 4, and 8, and every 4 cycles thereafter until PD, the EoT visit and the first safety follow-up visit 30 (± 3) days after the last dose of Dato-DXd in combination with durvalumab and Carboplatin
Safety objective
To assess the safety and tolerability of Dato-DXd in combination with durvalumab and carboplatin as compared with pembrolizumab in combination with platinum based chemotherapy in first-line treatment of participants with locally advanced or metastatic NSCLC.
Endpoints Variable
Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE Version 5.0), rates of AE-related dose discontinuations and modifications, and also in terms of:
ECOG PS.
Vital signs, physical examination and body weight.
Clinical chemistry, haematology, and urinalysis assessments.
ECG.
Ophthalmologic assessments
Target Sample Size
Total Sample Size="1000" Sample Size from India="36" 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, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)
Approximately 1000 patients will be randomized in a 1:1: ratio in 2 treatment arms
At study start, mandatory tumour samples will be collected for retrospective assessment of TROP2 expression in a sponsor-designated central laboratory using the TROP2 IHC clinical trial assay (Ventana Medical Systems, Inc., Tucson, Arizona) until prospective assay availability.
All the patients randomized into study will be followed for survival follow up.
Participants will be stratified based on tumour histology (squamous versus non-squamous), centrally determined PD-L1 expression (TC < 1%, TC 1% to 49%, and TC ≥ 50%), smoking status (current/former smoker versus never smoker) and TROP2 biomarker status (positive or negative) to ensure that there is a balanced distribution of these important prognostic/predictive factors between treatment arms.
Tumor evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to randomization); thereafter every 7 weeks ±1 week (after randomization) up to Week 12,then every 9 weeks (± 7 days) up to Week 48 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1-defined radiological PD plus an additional follow-up scan at least 4 weeks later and no later than the next scheduled imaging visit.
Follow-up of Participants Post Discontinuation of Study Intervention
After study intervention discontinuation, all participants will undergo an end-of-treatment visit (within 97 days of discontinuation) and will be followed up for safety assessments up to 97 days after their last dose of study intervention (ie, the safety follow-up visit). If the day of discontinuation is over 97 days from last study intervention administration, follow-up assessment is not needed.
Participants who have discontinued study intervention prior to objective RECIST 1.1-defined radiological progression will be followed up with tumour assessments as indicated in the SoA until the follow-up scan at least 4 weeks later and no later than the next scheduled imaging visit (if clinically feasible), or death regardless of whether or not the participant started a subsequent anti-cancer therapy unless they have withdrawn all consent to study-related assessments.
All participants will be followed up for survival status after intervention discontinuation every 3 months (± 7 days) until death, withdrawal of consent, or the end of the study, per the SoA. Participants will also be followed up for PFS2 after every 3 months (± 7 days) after initial objective PD until death, withdrawal of consent, or the end of the study, per the SoA.