Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen

NCT ID: NCT04549025

Last Updated: 2024-05-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-19
• Study Completion Date: 2024-04-25

Brief Summary

This is a Phase 2, open-label study to evaluate PD-1 inhibitor pimivalimab (JTX-4014) alone and in combination with vopratelimab (JTX-2011), an ICOS agonist, in biomarker-selected adult subjects with metastatic NSCLC who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum-based chemotherapy regimen.

Detailed Description

Pimivalimab is a fully human IgG4 monoclonal antibody designed to specifically bind to programmed cell death receptor protein-1 (PD-1) and block its interaction with its ligands, programmed cell death receptor protein-1 ligand 1 (PD-L1) and programmed cell death receptor protein-1 ligand 2 (PD-L2), to augment anti-tumor T cell activity. Vopratelimab is an agonist monoclonal antibody that specifically binds to the Inducible CO-Stimulator of T cells (ICOS) to generate an anti-tumor immune response. This is a Phase 2, open label study to evaluate the efficacy, safety, tolerability of pimivalimab alone and in combination with vopratelimab in biomarker-selected adult subjects with metastatic non-small cell lung cancer (NSCLC) who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum-based chemotherapy regimen.

Conditions

NSCLC

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Monotherapy Cohort 1 (MC1)

Enrolled patients will receive 1000 mg pimivalimab (JTX-4014) administered alone every 6 weeks (q6w).

Group Type: EXPERIMENTAL

Pimivalimab

Intervention Type: DRUG

Specified dose on specified days

Combination Therapy Cohort 1 (CC1)

For Cycle 1, enrolled patients will receive 0.1 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.

Group Type: EXPERIMENTAL

Pimivalimab

Intervention Type: DRUG

Specified dose on specified days

Vopratelimab

Intervention Type: DRUG

Specified dose on specified days

Combination Therapy Cohort 2 (CC2)

For Cycle 1, enrolled patients will receive 0.03 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.

Group Type: EXPERIMENTAL

Pimivalimab

Intervention Type: DRUG

Specified dose on specified days

Vopratelimab

Intervention Type: DRUG

Specified dose on specified days

Interventions

Pimivalimab

Specified dose on specified days

Intervention Type: DRUG

Vopratelimab

Specified dose on specified days

Intervention Type: DRUG

Other Intervention Names

JTX-4014; JTX-2011

Eligibility Criteria

Inclusion Criteria

1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures;

2. Histologically or cytologically confirmed diagnosis of NSCLC with evaluable or measurable disease according to RECIST v1.1 with at least 1 measurable lesion;

3. Confirmed tumor RNA signature score in accordance with the study protocol;

4. Previously treated for locally advanced or metastatic NSCLC with 1 prior systemic antineoplastic platinum-containing regimen. Regimen should consist of chemotherapy or with bevacizumab;

5. Age of ≥18 years;

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

7. Predicted life expectancy of ≥ 3months;

8. Specified laboratory values in accordance with the study protocol;

9. If with medical history of the following, eligibility should be discussed with the Medical Monitor:

1. Prior biliary tract disorders (based on Medical Dictionary for Regulatory Activities [MedDRA] system organ class of Hepatobiliary disorders and MedDRA high-level terms of Obstructive bile duct disorders, Hepatic vascular disorders, and Structural and other bile duct disorders);

2. Portal hypertension and/or hepatic vascular disorders;

10. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned Cycle 1, Day 1 (C1D1) and a negative urine or serum pregnancy test on C1D1. In addition, the WOCBP must be willing to complete a urine or serum pregnancy test prior to each dose of either study drug;

11. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration. Highly effective methods of birth control are defined as those that, alone or in combination, result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.

Exclusion Criteria

1. Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational;

2. Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting;

3. Chemotherapy <28 days prior to planned C1D1

4. Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor monoclonal antibody (mAb) at any time, including pimivalimab; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy;

5. Organ transplantation, including allogenic or autologous stem cell transplantation;

6. Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease):

1. Biologic therapy

2. Targeted therapy, with the exception of bevacizumab if administered in combination with a platinum-based chemotherapy regimen as first line treatment

7. Positive test for any of the following epidermal growth factor receptor gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q;

8. The following toxicity history:

1. Ongoing toxicity attributed to prior therapy that was Grade >1 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE); Exceptions: Grade >1 toxicities that, in the opinion of the Investigator, should not exclude the subject (e.g., alopecia, Grade 2 neuropathy, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement therapy) and are approved by the Medical Monitor;

2. History of pneumonitis or interstitial lung disease;

3. Symptomatic ascites or pleural effusion (subjects who are clinically stable for >3 months following treatment for these conditions [including therapeutic thoraco- or paracentesis] are eligible);

4. If with medical history of the following, eligibility should be discussed with the Medical Monitor: colitis, hepatitis, nephritis, skin reactions, or encephalitis;

9. Known severe intolerance or life-threatening hypersensitivity reactions to humanized mAbs or IV Ig preparations; any history of anaphylaxis; prior history of human anti-human antibody response; or known allergy to any of the study drugs (including their analogues or excipients [L-Histidine, mannitol, sodium chloride, or polysorbate 80]);

10. Major surgery (excluding minor procedures, e.g., placement of vascular access, gastrointestinal/biliary stent, and biopsy) < 4 weeks prior to planned C1D1;

11. Prior whole brain radiation;

12. Subjects with the following should be reviewed with the Medical Monitor prior to enrollment:

1. Brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation;

2. Radiation (other than whole brain radiation) has been or will be administered <21 days prior to planned C1D1;

13. Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis B, C, or human immunodeficiency virus (testing not required);

14. Women who are pregnant, breastfeeding, or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study;

15. Concurrent second malignancy;

16. An active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents at a dose of ≥10 mg/day of prednisone equivalent. Subjects who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism who are stable on hormone replacement therapy will not be excluded from the study;

17. Medical or social condition that, in the opinion of the Investigator, might place the subject at an increased risk, adversely affect compliance, or confound safety or other clinical study data interpretation;

18. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jounce Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stew Kroll

Role: STUDY_DIRECTOR

Jounce Therapeutics, Inc.

Locations

Minsk City Clinical Oncology Dispensary

Minsk, , Belarus

N. N. Alexandrov National Cancer Centre

Minsk, , Belarus

University Clinical Center of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Clinical Center University of Sarajevo

Sarajevo, , Bosnia and Herzegovina

Multiprofile Hospital for Active Treatment - Dobrich AD

Dobrich, , Bulgaria

Multiprofile Hospital for Active Treatment - Uni Hospital OOD

Panagyurishte, , Bulgaria

Complex Oncology Center Plovdiv

Plovdiv, , Bulgaria

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment Serdika EOOD

Sofia, , Bulgaria

Clinical Hospital Centre Osijek

Osijek, , Croatia

General Hospital Pula

Pula, , Croatia

University Hospital of Split

Split, , Croatia

Klinicki bolnicki centar Zagreb

Zagreb, , Croatia

Arensia Tbilisi - PPDS

Tbilisi, , Georgia

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, , Hungary

Bács-Kiskun Varmegyei Oktatokorhaz

Kecskemét, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

Pauls Stradins Clinical University Hospital

Riga, , Latvia

Riga East Clinical University Hospital, Latvian Oncology Center

Riga, , Latvia

Arensia Chisinau - PPDS

Chisinau, , Moldova

Affidea Romania SRL

Bucharest, , Romania

Prof Dr I Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta

Constanța, , Romania

Oncology Center Sfantul Nectarie

Craiova, , Romania

Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, , Russia

Chelyabinsk Regional Clinical Oncology Dispensary

Chelyabinsk, , Russia

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic

Kazan', , Russia

Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy

Krasnoyarsk, , Russia

Kursk Regional Oncology Centre

Kursk, , Russia

Vitamed Multidisciplinary Medical Center

Moscow, , Russia

Nizhniy Novgorod City Oncology Center

Nizhny Novgorod, , Russia

Clinical Oncology Dispensary

Omsk, , Russia

PMI Euromedservice

Pushkin, , Russia

Ryazan State Medical University n.a. I.P. Pavlov

Ryazan, , Russia

First St. Petersburg State Medical University n.a. I.P Pavlov

Saint Petersburg, , Russia

GBUZ St. Petersburg Clinical Research Center of Specialized Types of Care Oncology n.a. Napalkova

Saint Petersburg, , Russia

JSC "Current medical technologies"

Saint Petersburg, , Russia

Mordovia State University

Saransk, , Russia

Research Oncology Institute of Tomsk Scientific Center

Tomsk, , Russia

Volgograd Regional Clinical Oncology Dispensary

Volgograd, , Russia

Regional Clinical Oncology Hospital

Yaroslavl, , Russia

Clinical Hospital Center Bezanijska Kosa

Belgrade, , Serbia

Institute for Oncology and Radiology of Serbia - PPDS

Belgrade, , Serbia

University Clinical Center of Serbia - PPDS

Belgrade, , Serbia

Institute of Lung Diseases Vojvodina

Kamenitz, , Serbia

University Clinical Center Kragujevac

Kragujevac, , Serbia

Narodny onkologicky - PPDS

Bratislava, , Slovakia

Vychodoslovensky onkologicky ustav, a.s.

Košice, , Slovakia

Adana Sehir Egitim ve Arastirma Hastanesi

Adana, , Turkey (Türkiye)

Hacettepe University Medical Faculty Hospital

Ankara, , Turkey (Türkiye)

Akdeniz University Medical Faculty Hospital

Antalya, , Turkey (Türkiye)

Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi Hastane - Hematoloji Bilim Dali

Edirne, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty Hospital

Istanbul, , Turkey (Türkiye)

T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, , Turkey (Türkiye)

Izmir Ekonomi University Medical Point Hospital

Izmir, , Turkey (Türkiye)

Inonu University Faculty of Medicine Turgut Ozal Medical Center

Malatya, , Turkey (Türkiye)

Communal Nonprofit Enterprise Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of ChOC

Cherkasy, , Ukraine

Communal Nonprofit Enterprise City Clinical Hospital #4 of Dnipro City Council

Dnipro, , Ukraine

Municipal Nonprofit Enterprise SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC

Ivano-Frankivsk, , Ukraine

Arensia Kapitanivka - PPDS

Kapitanivka, , Ukraine

Communal Nonprofit Enterprise Regional Center of Oncology

Kharkiv, , Ukraine

SI Institute of Medical Radiology and Oncology n.a. S.P. Hryhoriev of NAMS of Ukraine

Kharkiv, , Ukraine

Communal Nonprofit Enterprise Khmelnytskyi Regional Antitumor Center of Khmelnytskyi Regional Council

Khmelnytskyi, , Ukraine

Private Enterprise Private Manufacturing Company Acinus

Kropyvnytskyi, , Ukraine

Clinic of National Institute of Cancer

Kyiv, , Ukraine

Communal Nonprofit Enterprise Kyiv City Clinical Oncological Center

Kyiv, , Ukraine

Kyiv Railway Clinical Hospital #3 of Branch Health Center of the PJSC Ukrainian Railway

Kyiv, , Ukraine

Medical Center of LLC ARENSIA Exploratory Medicine

Kyiv, , Ukraine

ME Volyn Regional Clinical Hospital of the Volyn Regional Council Regional Medical Oncology Centre

Lutsk, , Ukraine

Medical and diagnostic center of MediX-Ray International Group LLC Israeli Oncology Hospital LISOD

Obukhiv, , Ukraine

MNPE Central City Clinical Hospital of Uzhhorod City Council

Uzhhorod, , Ukraine

Countries

Belarus; Bosnia and Herzegovina; Bulgaria; Croatia; Georgia; Hungary; Latvia; Moldova; Romania; Russia; Serbia; Slovakia; Turkey (Türkiye); Ukraine

Other Identifiers

JTX-4014-202

Identifier Type: -

Identifier Source: org_study_id