CTRI

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CTRI Number

CTRI/2025/07/091069 [Registered on: 17/07/2025] Trial Registered Prospectively

Last Modified On:

01/04/2026

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Parallel Group Trial

Public Title of Study

This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non small Cell Lung Cancer With High Levels of PDL1.

Scientific Title of Study

An Open-Label, Randomized, Controlled Phase 3 Study of Sigvotatug Vedotin in Combination with Pembrolizumab Compared with Pembrolizumab Monotherapy as First-Line Treatment in Participants with PD-L1 High, more than 50 percent of Tumor Cells Expressing PDL1, Locally Advanced, Unresectable, or Metastatic Non Small Cell Lung Cancer

Trial Acronym

NIL

Secondary IDs if Any

Secondary ID	Identifier
2024-517968-36	EudraCT
C5751003, ver No 01, dated 06 Feb 2025	Protocol Number
NCT06758401	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	Dr Seema Pai
Designation	Sr Director Clinical Site Operations - India Cluster
Affiliation	Pfizer Limited
Address	The Capital, 1802-1901, Plot No. C-70, G Block Bandra Kurla Complex, Bandra East Mumbai MAHARASHTRA 400051 India
Phone	02266932000
Fax
Email	seema.Pai@pfizer.com

Details of Contact Person
Public Query

Name	Dr Seema Pai
Designation	Sr Director Clinical Site Operations - India Cluster
Affiliation	Pfizer Limited
Address	The Capital, 1802-1901, Plot No. C-70, G Block Bandra Kurla Complex, Bandra East MAHARASHTRA 400051 India
Phone	02266932000
Fax
Email	seema.Pai@pfizer.com

Source of Monetary or Material Support

Pfizer Inc. 66 Hudson Boulevard East New York, NY 10001 United States

Primary Sponsor

Name	Pfizer Inc.
Address	66 Hudson Boulevard East New York, NY 10001 United States
Type of Sponsor	Pharmaceutical industry-Global

Details of Secondary Sponsor

Name	Address
Pfizer Limited	The Capital, 1802-1901, Plot No. C-70 G Block, Bandra Kurla Complex, Bandra East, Mumbai City India - 400051

Countries of Recruitment

Argentina
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
Chile
China
Czech Republic
Denmark
Finland
France
Georgia
Germany
Greece
Hungary
India
Ireland
Israel
Italy
Japan
Mexico
Netherlands
Norway
Poland
Republic of Korea
Romania
Slovakia
Spain
Swaziland
Taiwan
Turkey
United Kingdom
United States of America

Sites of Study
Modification(s)

No of Sites = 8
Name of Principal Investigator	Name of Site	Site Address	Phone/Fax/Email
Dr Vamshi Krishna M	AIG Hospitals	Plot No 2/3/4/5, Survey No 136, 1, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032, India Hyderabad TELANGANA	9959778112 dr.vamshik@aighospitals.com
Dr Nirmal Raut	Bhakti Vedanta Hospital and Research Institute	1st floor, B wing, Main Building, Oncology Department, 3rd Floor Medical Research Department, Srishti complex, Bhaktivedanta Swami Marg, Mira Road, Thane East - 401107 Mumbai MAHARASHTRA	9930398156 drnirmalraut@gmail.com
Dr Chandragouda Dodagoudar	Dr B.L. Kapur Memorial Hospital	1st floor, OPD 9, Oncology Department, Pusa Road, New Delhi-110005, India New Delhi DELHI	91 9671004610 drchandru1976@yahoo.co.in
Dr Vineet Govinda Gupta	Fortis Hospital	A-Block, Shalimar Bagh, New Delhi- 110088, India. New Delhi DELHI	9911152107 vineet.gupta1@fortishealthcare.com
Dr Tushar Vishvasrao Patil	Sahyadri Super Speciality Hospital	First Floor, OPD 111, Plot No 30 – C Erandawane, Karve Road Pune – 411004 Mumbai MAHARASHTRA	919552522556 tussipats@hotmail.com
Dr Satheesh CT	Spandana Oncology Centre	Clinical Research Department, No. 919, New No. 68, 28th Main Road, 9th Block, Jayanagar, Bangalore-560069 Bangalore KARNATAKA	9242698750 drsatheeshct@gmail.com
Dr Kumar Prabhash	Tata Memorial Hospital	OPD No 204, 2nd Floor, Homi Bhabha Block,Dr. Ernest Borges Marg, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai 400012 Mumbai MAHARASHTRA	9167760576 kprabhash1@gmail.com
Dr Siddharth Kumar Sahai	Venkateshwar Hospital	Sector 18 A Dwarka New Delhi-110075, India. New Delhi DELHI	9899440409 siddharth.sahai@venkateshwarhospitals.com

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 8
Name of Committee	Approval Status
Bhaktivedanta Hospital Ethics Committee	Approved
Dr. B.L. Kapur Memorial Hospital Ethics Committee	Approved
IEC for Spandana Oncology Centre	Approved
IEC Venkateshwar Hospital Unit Of ASHA	Approved
Institutional Ethics Committee Asian Institute of Gastroenterology	Approved
Institutional ethics Committee IEC-I and IEC-II	Approved
Institutional Ethics Committee, Fortis Hospital	Approved
Sahyadri Hospitals Pvt Ltd Ethics Committee	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	Pembrolizumab	administered as an IV infusion once every 6 weeks
Intervention	Sigvotatug vedotin	administered as an IV infusion once every two weeks

Inclusion Criteria

Age From	18.00 Year(s)
Age To	65.00 Year(s)
Gender	Both
Details	1. Participants must meet the following criteria- -Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the AJCC Staging Manual, Version 8.0 and the UICC Staging System, Eighth edition. -Participants with non-squamous histology must have documented negative test results for EGFR, ALK, and ROS1 AGAs and no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies per local standard of care. -Large cell neuroendocrine carcinoma is excluded. -Candidate for treatment with pembrolizumab monotherapy per local guidelines. 2. Tumor has PD-L1 expression in more than 50 percent of tumor cells as determined by local testing 3. Measurable disease based on RECIST v1.1 per investigator. 4. Resolution of acute effects of any prior therapy to either baseline severity or NCI CTCAE Grade 1 or less (except for AEs not constituting a safety risk in the investigators judgment), unless otherwise excluded.

ExclusionCriteria

Details

1. Life expectancy of less than 3 months in the opinion of the investigator.
2. Any medical or psychiatric condition including recent, within the past year or active suicidal ideation or behavior or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.
3. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
4. Known or suspected hypersensitivity, intolerance, or contraindication to any excipient contained in the drug formulation of sigvotatug vedotin or pembrolizumab.
5. Participants with any of the following respiratory conditions:
- Evidence of noninfectious or drug-induced ILD or pneumonitis
- Known DLCO (adjusted for hemoglobin) less than 50 percent predicted.
-Pulmonary diseases of grade 3 or higher unrelated to underlying malignancy
6. Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and-or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter less than 0.5 cm are permitted.
7. Major surgery (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 21 days or minor surgery within 7 days prior to first dose of study intervention.
8. Receipt of a live vaccine within 30 days prior to first dose of study intervention.
9. Pre-existing peripheral neuropathy Grade 2 or higher as per NCI CTCAE v5.0.
10. Uncontrolled diabetes mellitus, defined as HbA1c equal to or more than 8.0 percent or HbA1c between 7.0percent and 8.0percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
11. Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, required a high-dose steroid taper (equal to or more than 0.5 mg/kg prednisone or equivalent per day) for more than2 weeks, or required treatment with systemic immunosuppressive therapy.
12. History of autoimmune disease that has required systemic treatment in the past 2 years
13. Participants with prior solid organ or bone marrow transplantation.
14. Currently receiving a high-dose steroid (more than 10 mg prednisone or equivalent per day) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant.
15. Prior and concomitant therapy:
Any prior treatment with MMAE-derived drugs or IB6 targeting agents.
Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.
-(Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred less than9 months after the last dose.
-Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred more than6 months after the last dose.
3.Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.
4.Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.
5.Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor
16.History of or current ongoing infection, including participants positive for active HIV, HBV, or HCV.
17.Severe uncontrolled cardiac or cerebrovascular condition within the previous 6 months

Method of Generating Random Sequence

Other

Method of Concealment

Other

Blinding/Masking

Open Label

Primary Outcome

Outcome	TimePoints
1. Overall survival 2. Progression Free Survival (PFS) assessed by blinded independent central review (BICR)	Approx 2 years

Secondary Outcome

Outcome	TimePoints
Progression Free Survival as assessed by Investigator	Approx 4 years
Objective Response Rate as assessed by BICR	Approx 4 years
Objective Response Rate as assessed by Investigator	Approx 4 years
Duration of Response as assessed by BICR	Approx 4 years
Duration of Response as assessed by Investigator	Approx 4 years
Number of participants with adverse events (AEs)	Approx 4 years
Pharmacokinetics (PK) of antibody-conjugated monomethyl auristatin E (ac-MMAE) in plasma- Plasma concentration at end of infusion (CEOI)	Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of ac-MMAE in plasma: Plasma predose concentration (Cpredose)	Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of unconjugated monomethyl auristatin E (MMAE) in plasma: Plasma concentration at end of infusion (CEOI)	Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of MMAE in plasma: Plasma predose concentration (Cpredose)	Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
Number of participants with antidrug antibodies (ADAs)	Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1

Target Sample Size

Total Sample Size="714"
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)

20/08/2025

Date of Study Completion (India)

Applicable only for Completed/Terminated trials

Date of First Enrollment (Global)

04/05/2025

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

The purpose of the study is to compare how the new combination treatment (Sigvotatug Vedotin plus pembrolizumab) works compared to pembrolizumab alone in patients with non-small cell lung cancer (NSCLC) with high levels of PD-L1. This is a protein that acts as a kind of brake to keep the body’s immune responses under control.

The study is seeking for participants who:

1. Are confirmed to have NSCLC (Stage 3 or 4)

2. Have PD-L1 levels in more than 50 percent of the cancer cells.

All participants in this study will receive pembrolizumab at the study clinic once every 6 weeks as an intravenous (IV) infusion (give directly into a vein). In addition, half of the participants will also receive Sigvotatug Vedotin once every 2 weeks as an IV infusion in addition to receiving pembrolizumab.

Participants may receive pembrolizumab for up to about two years. Those participants taking Sigvotatug Vedotin can continue until their NSCLC is no longer responding. The study team will monitor to see how each participant is doing with the study treatment during regular visits at the clinic.