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

NSCLC Clinical Trial

— SELECT  

Official title:

Phase 2 Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04549025
• Other study ID #: JTX-4014-202
• Status: Terminated
• Phase: Phase 2
• Start date: October 19, 2020
• Est. completion date: April 25, 2024

Study information

• Verified date: May 2024
• Source: Jounce Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 69
• Est. completion date: April 25, 2024
• Est. primary completion date: April 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• Pimivalimab
Specified dose on specified days
• Vopratelimab
Specified dose on specified days

Locations

Country	Name	City	State
Belarus	Minsk City Clinical Oncology Dispensary	Minsk
Belarus	N. N. Alexandrov National Cancer Centre	Minsk
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Clinical Center University of Sarajevo	Sarajevo
Bulgaria	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
Croatia	Clinical Hospital Centre Osijek	Osijek
Croatia	General Hospital Pula	Pula
Croatia	University Hospital of Split	Split
Croatia	Klinicki bolnicki centar Zagreb	Zagreb
Georgia	Arensia Tbilisi - PPDS	Tbilisi
Hungary	Veszprem Megyei Tudogyogyintezet	Farkasgyepu
Hungary	Bács-Kiskun Varmegyei Oktatokorhaz	Kecskemét
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga East Clinical University Hospital, Latvian Oncology Center	Riga
Moldova, Republic of	Arensia Chisinau - PPDS	Chisinau
Romania	Affidea Romania SRL	Bucharest
Romania	Prof Dr I Chiricuta Institute of Oncology	Cluj-Napoca
Romania	Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta	Constanta
Romania	Oncology Center Sfantul Nectarie	Craiova
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangel'sk
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan
Russian Federation	Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy	Krasnoyarsk
Russian Federation	Kursk Regional Oncology Centre	Kursk
Russian Federation	Vitamed Multidisciplinary Medical Center	Moscow
Russian Federation	Nizhniy Novgorod City Oncology Center	Nizhny Novgorod
Russian Federation	Clinical Oncology Dispensary	Omsk
Russian Federation	PMI Euromedservice	Pushkin
Russian Federation	Ryazan State Medical University n.a. I.P. Pavlov	Ryazan'
Russian Federation	First St. Petersburg State Medical University n.a. I.P Pavlov	Saint Petersburg
Russian Federation	GBUZ St. Petersburg Clinical Research Center of Specialized Types of Care Oncology n.a. Napalkova	Saint Petersburg
Russian Federation	JSC "Current medical technologies"	Saint Petersburg
Russian Federation	Mordovia State University	Saransk
Russian Federation	Research Oncology Institute of Tomsk Scientific Center	Tomsk
Russian Federation	Volgograd Regional Clinical Oncology Dispensary	Volgograd
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Serbia	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	University Clinical Center Kragujevac	Kragujevac
Serbia	Institute of Lung Diseases Vojvodina	Sremska Kamenica
Slovakia	Narodny onkologicky - PPDS	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav, a.s.	Košice
Turkey	Adana Sehir Egitim ve Arastirma Hastanesi	Adana
Turkey	Hacettepe University Medical Faculty Hospital	Ankara
Turkey	Akdeniz University Medical Faculty Hospital	Antalya
Turkey	Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi Hastane - Hematoloji Bilim Dali	Edirne
Turkey	Istanbul University Cerrahpasa Medical Faculty Hospital	Istanbul
Turkey	T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
Turkey	Izmir Ekonomi University Medical Point Hospital	Izmir
Turkey	Inonu University Faculty of Medicine Turgut Ozal Medical Center	Malatya
Ukraine	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-Frankivs'k
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	Luts'k
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

Sponsors (1)

Lead Sponsor	Collaborator
Jounce Therapeutics, Inc.

Countries where clinical trial is conducted

Belarus,  Bosnia and Herzegovina,  Bulgaria,  Croatia,  Georgia,  Hungary,  Latvia,  Moldova, Republic of,  Romania,  Russian Federation,  Serbia,  Slovakia,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in measurable lesion size	Mean percent change from baseline tumor size of all measurable existing and new lesions	over 9 and 18 weeks (average)
Secondary	Overall response rate (ORR)	ORR (percentage of subjects with complete response [CR] + partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	up to 24 months
Secondary	Progression-free survival (PFS)	PFS according to RECIST v1.1	up to 24 months
Secondary	Landmark PFS rate	Landmark PFS rate at 9 months according to RECIST v1.1	9 months
Secondary	Disease control rate (DCR)	DCR (confirmed CR + confirmed PR + unconfirmed stable disease [SD]) according to RECIST v1.1	up to 24 months
Secondary	Duration of response (DOR)	DOR in months according to RECIST v1.1	up to 24 months
Secondary	Overall survival (OS)		up to 24 months
Secondary	Treatment-emergent adverse events (TEAEs)	Incidence and grade of TEAEs	up to 24 months
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - Cmax (maximum observed concentration)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - Tmax (time of first occurrence of Cmax)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - AUClast (area under the concentration-time curve from time zero to the last measurable concentration)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - half-life (time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - clearance (efficiency of drug elimination)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Pharmacokinetic properties of pimivalimab and vopratelimab - volume of distribution (amount of drug in the body divided by the plasma drug concentration)		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Incidence of anti-drug antibodies (ADAs) to either pimivalimab or vopratelimab		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Incidence of neutralizing antibodies (NAbs) to either pimivalimab or vopratelimab		Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Secondary	Association of baseline tumor RNA signature score with clinical outcomes	Change in measurable lesion size for patients with elevated tumor RNA signature score (i.e., tumor inflammation signature (TIS) vopra score = 7.9)	up to 24 months