Clinical trial NCT04549025: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: NSCLC
Lead sponsor: Jounce Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in measurable lesion size
timeFrame: over 9 and 18 weeks (average)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: up to 24 months
measure: Progression-free survival (PFS)
timeFrame: up to 24 months
measure: Landmark PFS rate
timeFrame: 9 months
measure: Disease control rate (DCR)
timeFrame: up to 24 months
measure: Duration of response (DOR)
timeFrame: up to 24 months
measure: Overall survival (OS)
timeFrame: up to 24 months
measure: Treatment-emergent adverse events (TEAEs)
timeFrame: up to 24 months
measure: Pharmacokinetic properties of pimivalimab and vopratelimab - Cmax (maximum observed concentration)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Pharmacokinetic properties of pimivalimab and vopratelimab - Tmax (time of first occurrence of Cmax)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Pharmacokinetic properties of pimivalimab and vopratelimab - AUClast (area under the concentration-time curve from time zero to the last measurable concentration)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: 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%)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Pharmacokinetic properties of pimivalimab and vopratelimab - clearance (efficiency of drug elimination)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Pharmacokinetic properties of pimivalimab and vopratelimab - volume of distribution (amount of drug in the body divided by the plasma drug concentration)
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Incidence of anti-drug antibodies (ADAs) to either pimivalimab or vopratelimab
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Incidence of neutralizing antibodies (NAbs) to either pimivalimab or vopratelimab
timeFrame: Cycle 1 through Cycle 6 (each cycle is 6 weeks)
measure: Association of baseline tumor RNA signature score with clinical outcomes
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Dispensary
city: Minsk
country: Belarus
facility: N. N. Alexandrov National Cancer Centre
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Center University of Sarajevo
city: Dobrich
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Dobrich AD
city: Panagyurishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Uni Hospital OOD
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center Plovdiv
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Pula
country: Croatia
facility: General Hospital Pula
city: Split
country: Croatia
facility: University Hospital of Split
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
city: Tbilisi
country: Georgia
facility: Arensia Tbilisi - PPDS
city: Farkasgyepű
country: Hungary
facility: Veszprem Megyei Tudogyogyintezet
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Varmegyei Oktatokorhaz
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital, Latvian Oncology Center
city: Chisinau
country: Moldova, Republic of
facility: Arensia Chisinau - PPDS
city: Bucharest
country: Romania
facility: Affidea Romania SRL
city: Cluj-Napoca
country: Romania
facility: Prof Dr I Chiricuta Institute of Oncology
city: Constanţa
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta
city: Craiova
country: Romania
facility: Oncology Center Sfantul Nectarie
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Dispensary
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncology Centre
city: Moscow
country: Russian Federation
facility: Vitamed Multidisciplinary Medical Center
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod City Oncology Center
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Pushkin
country: Russian Federation
facility: PMI Euromedservice
city: Ryazan'
country: Russian Federation
facility: Ryazan State Medical University n.a. I.P. Pavlov
city: Saint Petersburg
country: Russian Federation
facility: First St. Petersburg State Medical University n.a. I.P Pavlov
city: Saint Petersburg
country: Russian Federation
facility: GBUZ St. Petersburg Clinical Research Center of Specialized Types of Care Oncology n.a. Napalkova
city: Saint Petersburg
country: Russian Federation
facility: JSC "Current medical technologies"
city: Saransk
country: Russian Federation
facility: Mordovia State University
city: Tomsk
country: Russian Federation
facility: Research Oncology Institute of Tomsk Scientific Center
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Dispensary
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia - PPDS
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia - PPDS
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Institute of Lung Diseases Vojvodina
city: Bratislava
country: Slovakia
facility: Narodny onkologicky - PPDS
city: Košice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav, a.s.
city: Adana
country: Turkey
facility: Adana Sehir Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty Hospital
city: Edirne
country: Turkey
facility: Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi Hastane - Hematoloji Bilim Dali
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty Hospital
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital
city: İzmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: İzmir
country: Turkey
facility: Izmir Ekonomi University Medical Point Hospital
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine Turgut Ozal Medical Center
city: Cherkasy
country: Ukraine
facility: Communal Nonprofit Enterprise Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of ChOC
city: Dnipro
country: Ukraine
facility: Communal Nonprofit Enterprise City Clinical Hospital #4 of Dnipro City Council
city: Ivano-Frankivs'k
country: Ukraine
facility: Municipal Nonprofit Enterprise SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC
city: Kapitanivka
country: Ukraine
facility: Arensia Kapitanivka - PPDS
city: Kharkiv
country: Ukraine
facility: Communal Nonprofit Enterprise Regional Center of Oncology
city: Kharkiv
country: Ukraine
facility: SI Institute of Medical Radiology and Oncology n.a. S.P. Hryhoriev of NAMS of Ukraine
city: Khmelnytskyi
country: Ukraine
facility: Communal Nonprofit Enterprise Khmelnytskyi Regional Antitumor Center of Khmelnytskyi Regional Council
city: Kropyvnytskyi
country: Ukraine
facility: Private Enterprise Private Manufacturing Company Acinus
city: Kyiv
country: Ukraine
facility: Clinic of National Institute of Cancer
city: Kyiv
country: Ukraine
facility: Communal Nonprofit Enterprise Kyiv City Clinical Oncological Center
city: Kyiv
country: Ukraine
facility: Kyiv Railway Clinical Hospital #3 of Branch Health Center of the PJSC Ukrainian Railway
city: Kyiv
country: Ukraine
facility: Medical Center of LLC ARENSIA Exploratory Medicine
city: Luts'k
country: Ukraine
facility: ME Volyn Regional Clinical Hospital of the Volyn Regional Council Regional Medical Oncology Centre
city: Obukhiv
country: Ukraine
facility: Medical and diagnostic center of MediX-Ray International Group LLC Israeli Oncology Hospital LISOD
city: Uzhhorod
country: Ukraine
facility: MNPE Central City Clinical Hospital of Uzhhorod City Council
Study officials:
affiliation: Jounce Therapeutics, Inc.
name: Stew Kroll
role: STUDY_DIRECTOR
References: