CTRI/2024/10/075387 [Registered on: 16/10/2024] Trial Registered Prospectively
Last Modified On:
04/08/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A Global Study of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for Participants With Metastatic Non-small Cell Lung Cancer
Scientific Title of Study
A Phase III, Two-Arm, Parallel, Randomized, Multi-Center, Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer (mNSCLC) (eVOLVE-Lung02)
Trial Acronym
eVOLVE-Lung02
Secondary IDs if Any
Secondary ID
Identifier
D798AC00001 Version Number: 1.0 Version Date: 06 July 2023
Protocol Number
NCT05984277
ClinicalTrials.gov
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
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
Bangalore 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
Bangalore 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
Argentina Australia Austria Belgium Belize Canada China Czech Republic France Germany Hungary India Italy Japan Mexico Netherlands Poland Republic of Korea Slovakia South Africa Spain Taiwan Thailand Turkey United Kingdom United States of America
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Srinivas K G
Bharat Hospital and Institute of Oncology
Dept. of Medical Oncology
#438, 1st Stage, Outer Ring Road, Hebbal Industrial Area, Lakshmikanth Nagar, Mysuru – 570017, Karnataka, India Mysore KARNATAKA
9663121728
drsrinivaskg2020@gmail.com
Dr Deepak Koppaka
CARE Hospitals
Dept. of Medical Oncology
Hi- Tech City, Near Cyberbad Police Commissionerate, Hyderabad - 500032, Telangana, India Hyderabad TELANGANA
9052289998
drdeepak.koppaka@gmail.com
Dr Shruti Kate
HCG Manavata Cancer Centre
Dept. of Medical Oncology
Behind Shivang Auto, Mumbai Naka,
Nashik 422002, Maharashtra, India
Nashik MAHARASHTRA
7506117343
drshruti@mcrinasik.com
Dr Sameer Shrirangwar
KIMS - KINGSWAY HOSPITALS
Dept. of Medical Oncology
44, Parwana Bhawan, Kingsway, Nagpur-440001, Maharashtra, India Nagpur MAHARASHTRA
9833633299
dr.sameer.mdmed@gmail.com
Dr Akhil Kapoor
Mahamana Pandit Madan Mohan Malviya Cancer Centre
A Unit of Department of Atomic Energy, Govt. of India) Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus, Varanasi -221005, Uttar Pradesh, India Varanasi UTTAR PRADESH
9950482121
kapoorakhil1987@gmail.com
Dr Poulami Basu
Netaji Subhas Chandra Bose Cancer Hospital
Dept. of Medical Oncology
3081 Nayabad, New Garia, Kolkata – 700094, West Bengal, India Kolkata WEST BENGAL
8902444454
poulamibasu18386@gmail.com
Dr Chandrakant M V
NH-Rabindranath Tagore International Institute of Cardiac Sciences
Dept. of Medical Oncology
124 Eastern Metropolitan Bypass Premises No: 1489, Mukundapur Kolkata-700099, West Bengal, India Kolkata WEST BENGAL
7003206633
drmvch@gmail.com
Dr Lokesh K N
Radhakrishna Multispeciality Hospital
Dept. of Medical Oncology
Sunrise Towers, JP Road, Girinagar, Banashankari 3rd Stage, Bengaluru-560085, Karnataka, India Bangalore KARNATAKA
8971609070
knloki@gmail.com
Dr Amrith B P
Rajiv Gandhi Cancer Institute and Research Centre
Dept. of Medical Oncology
Sir Chotu Ram Marg, Rohini Institutional Area, Sector 5, Rohini, New Delhi - 110085, Delhi, India New Delhi DELHI
9481808245
amrithpatel@gmail.com
Dr Kaushal Kalra
Vardham Mahavir Medical College and Safdarjung Hospital
Dept. of Medical Oncology
H693+H6W, NH 48, near AIIMS Hospital, Ansari Nagar West, New Delhi – 110029, Delhi, India New Delhi DELHI
Inclusion Criteria
Participant must be 18 years at the time of screening.
All races, genders, and ethnic groups are eligible for this study.
Histologically or cytologically documented squamous or non-squamous NSCLC.
Stage IV NSCLC not amenable to curative surgery or radiation.
Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion
and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and
ALK and ROS1 rearrangements.
Absence of documented tumor genomic alteration results from tests conducted as part of
standard local practice in any other actionable driver oncogenes for which there are locally approved targeted first-line therapies.
Provision of tumor sample during screening to assess the PD L1 status, confirmed by a
central reference laboratory using the VENTANA PD-L1 (SP263) Assay. All participants
must be able to undergo a fresh tumor biopsy during screening or to provide an available
tumor sample taken 3 months prior to screening for analysis.
Tumor PD L1 TC expression 50 percentage as determined using the VENTANA PD-L1 (SP263)
Assay by a central reference laboratory. PD-L1 status must be known prior to
randomization. Participants with PD-L1 TC 50 percentage or indeterminate/unevaluable result
are not eligible for the study.
At least one measurable lesion not previously irradiated, that can be accurately assessed at baseline
ECOG performance status 0 or 1
Life expectancy 12 weeks.
Adequate organ and bone marrow function
Body weight 35 kg at screening and randomization.
Contraceptive use by participants should be consistent with local regulations regarding
the methods of contraception for those participating in clinical studies.
Capable of giving signed informed consent.
Provision of signed and dated written Optional Genetic Research Information informed
consent
ExclusionCriteria
Details
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1 Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare
subtypes (eg, NUT carcinoma, thoracic SMARCA4-deficient undifferentiated tumor,
adenoid cystic carcinoma, epithelial-myoepithelial carcinoma) are excluded.
2 Spinal cord compression.
3 Brain metastases unless asymptomatic, stable, and not requiring steroids for at least
14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed
between the end of whole brain radiotherapy and study enrollment.
4 History of another primary malignancy except for:
(a) 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.
(b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
(c) Adequately treated carcinoma in situ without evidence of disease.
5 As judged by the investigator, any condition that would interfere with evaluation of the
study intervention or interpretation of participant safety or study results.
6 Evidence of the following infections:
(a) Active infection including tuberculosis (TB) (clinical evaluation that includes clinical
history, physical examination, and radiographic findings and TB testing in line with
local practice),
(b) Known human immunodeficiency virus (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 for 6 months, CD4 Plus count of 500 cells/μL,
stable for at least 6 months on the same anti-HIV medications, and no history of
AIDS (either CD4 Plus T cell count 200 cells/μL and/or AIDS-defining opportunistic
infection),
(c) or active or uncontrolled hepatitis B (HBV) or hepatitis C (HCV); Participants are
eligible if they:
Have controlled hepatitis C viral load defined as undetectable hepatitis C RNA
by PCR either spontaneously or in response to a successful prior course of
anti-hepatitis C therapy
- Have received HBV vaccination with only anti-HBs positivity and no clinical
signs of hepatitis
- Are HBsAg- and anti-HBc Plus (ie, those who have cleared HBV after infection)
and meet conditions i-iii below:
Are HBsAg with chronic HBV infection (lasting 6 months or longer) and
meet conditions i-iii below:
(i) HBV DNA viral load 100 IU/mL
(ii) Have normal transaminase values, or, if liver metastases are present,
abnormal transaminases, with a result of AST/ALT 3 ULN, which are
not attributable to HBV infection
(iii) Start or maintain antiviral treatment if clinically indicated as per the
investigator
(d) or active hepatitis A
7 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, 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.
8 History of primary active immunodeficiency.
9 Active or prior documented autoimmune or inflammatory disorders including
inflammatory bowel disease eg colitis or Crohns 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
hormone replacement.
(c) Any chronic skin condition that does not require systemic therapy.
(d) Participants without active disease in the last 5 years prior to enrolment may be
included.
(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 judgement with cardiologist consultation recommended.
11 Medical contraindication to platinum-based doublet chemotherapy.
Prior/Concomitant Therapy
12 Prior exposure to immune-mediated therapy including, but not limited to, other
anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic
anticancer vaccines.
13 Prior chemotherapy or any other systemic therapy for Stage IV NSCLC. Participants who
have received prior platinum-containing adjuvant, neoadjuvant, or definitive
chemoradiation for advanced disease are eligible, provided that progression has occurred
12 months from end of last therapy.
14 Persistent toxicities (CTCAE Grade 2) caused by previous anticancer therapy,
excluding alopecia. 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).
15 Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related
conditions (eg, insulin for diabetes, HRT, gonadotropin-releasing hormone analogs, and
bisphosphonates) is acceptable.
16 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.
17 Any concomitant medication known to be associated with Torsades de pointes.
18 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 palliative purpose (eg, pain
control).
19 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
20 Major surgical procedure (excluding placement of vascular access) or significant
traumatic injury within 4 weeks prior to the first dose of study intervention or still
recovering from prior surgery.
Note: Local surgery of isolated lesions for palliative intent is acceptable.
21 Receipt of live attenuated vaccine within 30 days prior to the first dose of study
intervention.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Dual Primary
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS in participants where PD-L1 TC 1%.
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS in participants where PD-L1 TC 1%.
PFS Measured by HR
Time Frame: upto approx. 57 months
OS Measured by HR
Time Frame: upto approx. 57 months
Secondary Outcome
Outcome
TimePoints
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS in all randomized participants.
The measure of interest is the HR of PFS.
[Time Frame: upto approx. 57 months]
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS in all randomized participants.
The measure of interest is the HR of OS.
[Time Frame: upto approx. 57 months]
To demonstrate and characterize the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS landmarks.
The measures of interest are the landmarks of PFS6, PFS12, PFS18, and PFS24.
[Time Frame: upto approx. 57 months]
To demonstrate and characterize the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS landmarks.
The measures of interest are the landmarks of OS12, OS18, OS24, and OS36.
[Time Frame: upto approx. 57 months]
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by investigator assessment of PFS.
PFS by investigator assessment, in participants with PD-L1 TC 1 percentage and in all randomized participants.
[Time Frame: upto approx. 57 months]
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of ORR in participants
ORR in participants with PD-L1 TC 1 and in all randomized participants.
[Time Frame: upto approx. 57 months]
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of DoR in participants.
DoR in participants with PD-L1 TC 1 percentage and in all randomized participants.
[Time Frame: upto approx. 57 months]
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS2 in participants.
PFS2 in participants with PD-L1 TC 1 percentage and in all randomized participants.
[Time Frame: upto approx. 57 months]
To assess the PK of volrustomig.
Concentration of volrustomig in serum and PK parameters (such as peak concentration and trough, as data allow; sparse sampling).
[Time Frame: upto approx. 57 months]
To investigate the immunogenicity of volrustomig
Presence of ADAs against volrustomig in serum (confirmatory results: positive or negative, titers).
[Time Frame: upto approx. 57 months]
To assess participant-reported functioning and HRQoL in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy
Change from baseline and TTD of functioning and overall global health status/QoL scores
[Time Frame: upto approx. 57 months]
To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.
To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.
To assess participant-reported pulmonary symptoms of mNSCLC in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.
TTD in pulmonary symptoms as measured by the NSCLC SAQ.
[Time Frame: upto approx. 57 months]
To assess the safety and tolerability of volrustomig plus chemotherapy compared with pembrolizumab plus chemotherapy in participants with mNSCLC.
Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE version 5.0), vital signs, clinical laboratory assessments, physical examinations, and electrocardiograms.
[Time Frame: upto approx. 57 months]
Target Sample Size
Total Sample Size="900" Sample Size from India="40" 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, randomized, multicenter study of volrustomig plus chemotherapy versus active comparator pembrolizumab plus chemotherapy as a 1L treatment for participants with mNSCLC and PD-L1 expression on less than 50 percentage of tumor cells (PD-L1 TC< 50 percentage). This study will be conducted in approximately 230 sites across 30 countries. Participants must have tumors that lack EGFR mutations and ALK and ROS1 rearrangements; in addition, tumors must not have any documented actionable genomic alterations identified by local standard practice for which there are locally approved 1L targeted therapies. During the 28-day screening period, mandatory tumor samples will be collected for prospective assessment of PD-L1 as measured using the VENTANA PD-L1 (SP263) Assay via a central reference laboratory. Only participants in the PD-L1 TC< 50 percentage population will be eligible to continue in the study. Following screening, eligible participants will be randomized 1:1 to either volrustomig plus chemotherapy or pembrolizumab plus chemotherapy; randomization will be stratified by histology, PD-L1 status, smoking history, and region of enrollment. At least 600 of the 900 randomized participants must be PD-L1 TC< 1 percentage; the remainder will be PD-L1 TC 1 percentage to 49 percentage. After the last dose of study intervention, all participants will undergo an end-of-treatment visit (within 21 [+ 7 days] of discontinuation) 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). In addition, all participants will be followed up for survival status after discontinuation of study intervention every 56 days (8 weeks) ± 14 days up to 3 years and then every 84 days (12 weeks) ± 14 days thereafter from the date of discontinuation until death, withdrawal of consent, or the end of the study.