CTRI/2025/05/086220 [Registered on: 02/05/2025] Trial Registered Prospectively
Last Modified On:
02/02/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Evixapodlin Monotherapy in Advanced Non-Small Cell Lung Cancer
Scientific Title of Study
Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Evixapodlin
Administered as 2nd Line Monotherapy in Subjects with Advanced
Non-Small Cell Lung Cancer Expressing PD-L1
Trial Acronym
EVIX-M
Secondary IDs if Any
Secondary ID
Identifier
OX-4224-200; Amendment 2 : 05 Feb 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Kishor Khotkar
Designation
Sr. Medical Monitor
Affiliation
KlinEra Global Services
Address
801, Neelkanth Corporate Park, Near Vidyavihar Station, Vidyavihar West, Mumbai
Mumbai MAHARASHTRA 400086 India
Phone
7506369695
Fax
912225091476
Email
kishor.khotkar@klinera.com
Details of Contact Person Scientific Query
Name
Dr Kishor Khotkar
Designation
Sr. Medical Monitor
Affiliation
KlinEra Global Services
Address
801, Neelkanth Corporate Park, Near Vidyavihar Station, Vidyavihar West, Mumbai
Mumbai MAHARASHTRA 400086 India
Phone
7506369695
Fax
912225091476
Email
kishor.khotkar@klinera.com
Details of Contact Person Public Query
Name
Gaurav Kadam
Designation
Clinical Project Manager
Affiliation
KlinEra Global Services
Address
801, Neelkanth Corporate Park, Near Vidyavihar Station, Vidyavihar West, Mumbai
Mumbai MAHARASHTRA 400086 India
Phone
9967155123
Fax
912225091476
Email
gaurav.kadam@klinera.com
Source of Monetary or Material Support
OmRx Oncology, Inc.
Primary Sponsor
Name
OmRx Oncology, Inc.
Address
2033 Gateway Place, Suite 500,
PMB #704, San Jose, California, USA 95110
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
KlinEra Global Services
801- 802, Neelkanth Corporate Park, Near Vidyavihar Station, Vidyavihar West Mumbai - 400086
ACE Hospital & Research Centre S.No. 32/2A,Gulwani Maharaj Road near abhishek, Pandurang colony, Erandwane, Pune, Maharashtra Pune MAHARASHTRA
9552522556
tussipats@hotmail.com
Dr Amit Sherawat
All India Institute of Medical Sciences
All lndia institute of Medical Sciences Veerbhadra Marg, Rishikesh, Uttarakhand, 249203 Dehradun UTTARANCHAL
9958474477
amit.monc@aiimsrishikesh.edu.in
Dr Pritanjali Singh
All India Institute of Medical Sciences
All India Institute of Medical Sciences, Patna - Aurangabad Rd, Phulwari Sharif, Patna - 801507 Patna BIHAR
9334931395
drpritanjalis@gmail.com
Dr Sachin Khurana
All India Institute of Medical Sciences
Room No. 160 A, Dr. B. R. Ambedkar Institute of Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029 New Delhi DELHI
Basavatarakma Indo-American Cancer Hospital & Research Institute
Basavatarakam Indo American Cancer Hospital And Research Institute, Road No.10, Banjara Hills, Hyderabad- 500034 Hyderabad TELANGANA
7021538508
pinninti.rakesh@gmail.com
Dr Kalyan Kusum Mukherjee
Chittaranjan National Cancer Institute
37, S.P Mukherjee Road. Kolkata-700026. West Bengal, India. Kolkata WEST BENGAL
9830115905
kkmukherjee4u@hotmail.com
Dr Minish Jain
CIMETS Inamdar Multispeciality Hospital, Pune
S.No 15, Fatima Nagar, Behind KPCT Mall, Pune 411040 Pune MAHARASHTRA
9823133390
drminishjain@yahoo.in
Dr Chetan Deshmukh
Deenanath Mangeshkar Hospital & Research Center
LMMFs Deenanath Mangeshkar Hospital & Research Center, Erandwane, Pune-411004 Pune MAHARASHTRA
9850811449
drchetandeshmukh@gmail.com
Dr Neeharika Alapati
Homi Bhabha Cancer Hospital & Research Centre
Homi Bhabha Cancer Hospital & Research Centre, Near Varun Motors, Aganampudi Village, Gajuwaka Mandalam, Vishakhapatnam, Andhra Pradesh, 530053. Visakhapatnam ANDHRA PRADESH
7799128889
drneehaganga@gmail.com
Dr Pratap Kishore Das
Indraprastha Apollo Hospitals
Indraprastha Apollo Hospitals, Sarita Vihar, Delhi - Mathura Road, New Delhi-110076. New Delhi DELHI
9810444600
drpratapdas@gmail.com
Dr Sunil Choudhary
Institute of Medical Sciences
Department of Radiotherapy and Radiation Medicine: Institute of Medical Sciences,Banaras Hindu University. Varanasi-22 1005. Uttar Pradesh. India Varanasi UTTAR PRADESH
9559481453
drsunil104@gmail.com
Dr Akhil Kapoor
Mahamana Pandit Madan Mohan Malviya Cancer Center
Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus, Varanasi-221005, Uttar Pradesh, India. Varanasi UTTAR PRADESH
9950482121
akhil@mpmmcc.tmc.gov.in
Dr Krishna Kumar Rathnam
Meenakshi Mission Hospital & Research Centre
Department of Oncology, Meenakshi Mission Hospital & Research Centre, Lake Area, Melur Road, Madurai-625107 Madurai TAMIL NADU
9380417299
kkrathnam@gmail.com
Dr Radhika Parimkayala
MNJ Institute of Oncology& Regional Cancer Center
MNJ Institute of Oncology& Regional Cancer Center-Red Hills, Lakadikapool, Hydrabad, Telangana Hyderabad TELANGANA
9848792682
radhika.parimkayala@gmail.com
Dr Sateesh CT
Spandana Oncology Centre
919, New No. 68, 28th Main Road, 9th Block, Jayanagar, Bangalore - 560069 Bangalore KARNATAKA
9242698750
drsateeshct@gmail.com
Dr Ajay Yadav
Sri Ram Cancer & super specialty Centre, Mahatma Gandhi Medical College & hospital
Sri Ram Cancer & super specialty Centre, Mahatma Gandhi Medical College & hospital, RIICO Industrial area, Jaipur, Rajasthan Jaipur RAJASTHAN
8826914083
ajayalwar01@gmail.com
Dr Neha Gupta
Swami Harshankranand Ji Hospital & Research Centre
Swami Harshankranand Ji Hospital & Research Centre, N8/237 Newada, B.H.U.- D.L.W. Road, Sunderpur, Varanasi. Varanasi UTTAR PRADESH
8004354185
drneha_500@yahoo.com
Dr Minit Shah
Tata Memorial Centre
Tata Memorial Centre Dr E Borges Road Parel Mumbai-400012 Mumbai MAHARASHTRA
9892640668
minitjshah@gmail.com
Dr Kaushal Kalra
VMMC and Safdarjung Hospital
VMMC and Safdarjung Hospital, New Delhi,110029 New Delhi DELHI
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centre
Approved
Institutional Ethics Committee, Institute of Medical Sciences
Approved
Institutional Ethics committee-Mahatma Gandhi Medical College & hospital
Approved
Institutional Ethics committee-VMMC&SIH
Approved
MNJIORCC Ethics Committee
Approved
Shubham Sadbhavna Ethics Committee
Approved
Spandana Oncology Center
Approved
Regulatory Clearance Status from DCGI
Status
No Objection Certificate
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
Evixapodlin
1000 mg dose - two 500 mg tablets QD
Intervention
Evixapodlin
500 mg dose - one 500 mg tablet QD
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. 18 to 75 years of age, inclusive at the time of signing informed consent form (ICF).
2. Voluntarily agreed to participate in this study by providing a signed, dated and ethics committee (EC) approved ICF before any protocol directed screening procedures are performed.
3. Capable of understanding and complying with protocol requirements, including daily compliance with administration of investigational medication, ability to travel to study visits and radiology appointments (in the opinion of the Investigator)
4. Regionally advanced, unresectable, histologically or cytologically documented, Stage IIIB or Stage IV NSCLC, who have recurrence or progression during or after one prior platinum containing chemotherapy regimen for advanced or metastatic disease.
5. At least one measurable non central nervous system NSCLC lesion qualifying as measurable disease per RECIST based on assessment by central radiologist
6. Tumor PD L1 high expression with one of the prespecified commercial IHC assays above the defined threshold.
7. Subjects must agree to provide a fresh biopsy sample or sufficient archival tumor tissue for Screening Period testing if (1) PD L1 expression or (2) AGA results for ALK or ROS rearrangement, EGFR mutations, are not available in the participants medical record.
8. At least 28 days must have elapsed since the last thoracic surgery and subjects should have recovered from all associated toxicities by the time of the first planned dose of study medication (Baseline C1D1).
9. The last dose of prior, systemic, anti cancer therapy must have been administered grater than or equal to 21 days prior to Baseline (C1D1), with the exception being TKIs approved for treatment of NSCLC have to be discontinued greater than or equal to 7 days prior to Baseline (C1D1).
10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at Screening and pre dose at Baseline, prior to the first dose of study medication.
11. Life expectancy greater or equal to 3 months, as assessed by Investigator (at Screening and at Baseline prior to first dose of study medication).
12. Negative serum pregnancy test for female subjects who are of childbearing potential within 14 days prior to the first dose of study drug at Baseline or be of non childbearing potential defined as postmenopausal or be surgically sterile (as documented in the medical record).
13. Female subjects of childbearing potential must agree to use protocol specified method(s) of contraception.
14. Females who are nursing must agree to permanently discontinue nursing (breastfeeding) before the first dose of evixapodlin.
15. Male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study, for 90 days following the last dose of study, and must agree to use protocol specified method(s) of contraception.
16. Subjects must have body weight 30 kg and may not present with severe weight loss (greater than 10 percent) within 6 weeks prior to randomization at Baseline Visit (based on subject self report and Investigator judgment).
ExclusionCriteria
Details
1. NSCLC diagnosis with positive AGA for ALK or ROS rearrangement, or EGFR mutations.
2. Known history of an additional malignancy likely to interfere with NSCLC treatment.
3. Toxicity from prior therapy without demonstrating sufficient recovery.
4. Prior treatment with immune modulators, including prior treatment with evixapodlin or another investigational oral checkpoint inhibitor.
5. Central nervous system (CNS) metastases that are symptomatic or require treatment and/or carcinomatous meningitis (i.e., leptomeningeal metastasis).
6. Received thoracic radiation within 3 months of Baseline (the first planned dose of study medication (C1D1)) and any concurrent or planned palliative radiotherapy.
7. Pregnant
8. Participation in another interventional clinical study while receiving evixapodlin.
9. Major medical conditions that might affect study participation (e.g., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled serious infection).
10. Impaired cardiac function, or clinically significant cardiac disease, or clinically important abnormalities in conduction or morphology of resting ECG at Screening, including:
a. Unstable angina
b. Myocardial infarction within 6 months prior to screening
c. New York Heart Association Class II or greater congestive heart failure
d. Uncontrolled hypertension
e. Poorly controlled arrhythmias within the last 6 months of first dose of study drug
f. Clinically important abnormalities in conduction defined as corrected QT interval by Fridericia method (QTcF) ≥450 msec in men, ≥470 msec in women.
11. History or evidence of interstitial lung disease including noninfectious pneumonitis, hypersensitivity pneumonitis OR a history of pneumonitis that required oral or IV steroids OR pulmonary conditions such as clinically significant sarcoidosis, silicosis, or idiopathic pulmonary fibrosis.
12. Symptomatic pleural effusion.
13. Stroke or transient ischemic attack or seizure disorder within 6 months prior to Screening.
14. Gastrointestinal (GI) or bowel conditions, surgery or symptoms that may affect drug absorption,
a. GI surgery within 6 weeks of Screening
b. GI symptoms of nausea, diarrhoea, or vomiting greater than CTCAE Grade 1 at time of Screening or at first dose of study drug or that in the opinion of the Investigator will interfere with study participation.
c. Risk factors for bowel obstruction or bowel perforation (e.g., acute diverticulitis)
d. Abdominal carcinomatosis
15. Active autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Bells palsy, Guillain Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
16. Subjects with a diagnosis of endocrine deficiencies who have not been stabilized on replacement therapy (e.g., thyroid replacement) prior to Screening
17. Subjects with Type 1 diabetes mellitus, or Type 2 diabetes mellitus with HbA1c ≥9% at Screening
18. Inability to discontinue sulfonylureas (e.g., glipizide, glyburide), be safely switched to another hypoglycemic agent (e.g. sitagliptin or another DPP4 inhibitor) and be on stable dose for at least 14 days before Baseline (C1D1)
19. Receipt of chronic systemic steroid therapy at daily dose exceeding 10 mg/day of prednisone or equivalent within 14 days of first planned dose of study medication (C1D1).
20. Active infection requiring use of systemic antibiotic therapy for more than 7 days within 28 days of first planned dose of study medication (C1D1).
21. History of any substance use disorder or alcohol use disorder in the past 2 years, as based on the diagnostic criteria in the Diagnostic and Statistical Manual Fifth Edition
22. History of organ transplantation, including allogeneic stem cell transplantation.
23. Received a live attenuated vaccine within 28 days of first planned dose of study medication at Baseline (C1D1).
24. History of immunodeficiency, AIDS or an HIV positive result on p24Ag/Antibody test at Screening
25. Acute or chronic HBV infection based on serology at Screening.
26. Hepatitis C Virus (HCV) infection based on positive anti-HCV antibody and presence of HCV RNA at Screening.
27. Concomitant use of strong cytochrome P450 (CYP)3A4 inhibitors, including but not limited to ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole.
28. Inability to discontinue warfarin, be safely switched to another anticoagulant (e.g., dabigatran or low molecular weight heparin), be on stable dose for at least 14 days before Baseline (C1D1) and have PT or aPTT values within therapeutic range of intended use of anticoagulants.
29. Concomitant use of herbal medication and ayurvedic preparations is prohibited due to cytochrome P450 inhibitory and liver toxicity potential.
30. Use of an investigational agent ≥28 days or 5-half-lives, whichever is greater, prior to Baseline (C1D1)
31. Any condition that, in the opinion of the Investigator, may interfere with the conduct or interpretation of the current study.
32. Absence of adequate organ function based on having central laboratory values outside the parameters defined in the protocol at Screening.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To determine the
overall response rate
(ORR) to evixapodlin
in NSCLC
Week 96
Secondary Outcome
Outcome
TimePoints
To determine the
disease control rate
(DCR) to evixapodlin
in NSCLC
Week 6
To determine overall
survival (OS) and
radiographic
progression free
survival (rPFS)
Week 96
To determine the safety
of evixapodlin in
advanced NSCLC
Week 96
To characterize the
pharmacokinetic (PK)
profile of evixapodlin
in subjects with
NSCLC
Baseline, Week 2, Week 8 and Week 16
To evaluate the change
in circulating tumor
DNA (ctDNA) over
time
Baseline and Week 8
Target Sample Size
Total Sample Size="50" Sample Size from India="50" 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
Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies across a range of immunogenic cancers. PD-1 is a receptor expressed on the surface of T cells, B cells and NK cells. One of its ligands, programmed cell death protein ligand 1 (PD-L1), is a cell surface protein found on different cell types including tumor cells. Blocking the PD-1 to PD-L1 interaction with monoclonal antibodies (mAb) results in anti-tumor response. Approved immune checkpoint inhibitors (ICIs) for cancer treatment include numerous antibodies to PD-1 and to PD-L1.
Evixapodlin is an orally bioavailable, small-molecule administered once daily that induces the homodimerization of PD-L1 and prevents binding to its receptor, PD-1. As a novel small molecule inhibitor of PD-L1, evixapodlin exhibits an on-target selectivity profile comparable with PD-L1 antibodies. The mechanism of action of evixapodlin results in potent and rapid PD-L1 occupancy on tumor cells that are expressing high levels of PD-L1 (PD-L1 high), versus on peripheral immune cells that are expressing basal levels of PD-L1 (PD-L1 low). This unique feature may translate to an improved therapeutic index in patients with PD-L1 high tumors.
Oral, small molecule PD-L1 inhibitors such as evixapodlin hold advantages over monoclonal antibodies providing an opportunity to expand access to ICI therapy for cancer patients both as monotherapy and combination therapy. Advantages include faster and more complete tumor penetration that could translate to better efficacy. The higher potency of evixapodlin on PD-L1 high tumors compared to PD-L1 low peripheral immune cells may translate to an improved therapeutic index compared to existing antibodies that saturate PD-L1 (or PD-1) irrespective of cellular expression level. The relatively short effective half-life of evixapodlin (17 hours) versus antibodies (~20 days) may translate to shorter lasting and easier-to-treat immune-related AE (irAE). Oral administration offers the potential for adjustable dosing regimens, convenience, elimination of the requirement for infusion facilities and staffing, and reduced complexity in manufacturing, transportation, storage and administration. These advantages also translate into opportunities for simplified combination therapies with other oral oncology agents.
Evixapodlin, also known as OX-4224, was previously under development by Gilead Sciences as GS-4224 and is currently being developed by OmRx Oncology, Inc.; it is supplied in the bisfumarate salt form. To provide efficacy and safety information in a tumor type highly responsive to ICI, this multicenter, open-label, randomized, Phase 2 study of evixapodlin will be conducted in subjects with advanced NSCLC expressing high tumor levels PD-L1 who progressed after first-line platinum-based chemotherapy. The planned study will enroll participants in India.