| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Non Small Cell Lung Cancer (NSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Lung cancer that has spread to other parts of the body |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059515 |
| E.1.2 | Term | Non-small cell lung cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To demonstrate superiority of the combination of JTX-4014 with vopratelimab over JTX-4014 monotherapy in biomarker-selected subjects |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate efficacy as measured by ORR, PFS, landmark PFS at 9 months, disease control rate, duration of response, and OS
• To evaluate the safety and tolerability of JTX-4014 alone and in combination with vopratelimab
• To evaluate the PK of JTX-4014 and vopratelimab
• To assess the immunogenicity of JTX-4014 and vopratelimab
• To evaluate association of baseline tumor RNA signature score with clinical outcomes |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 (TISVopra) score ≥ 7.9
4.Previously treated for locally advanced or metastatic NSCLC with 1
prior systemic antineoplastic platinum-containing regimen. Regimen
should consist of chemotherapy with or without bevacizumab.
5. Age of ≥ 18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Predicted life expectancy of ≥ 3 months
8. The following laboratory values:
a. Hemoglobin ≥ 9.0 g/dL
b. Platelet count ≥ 75 × 109 cells/L
c. Absolute neutrophil count > 1.5 × 109 and < 10 × 109 cells/L
d. Serum creatinine < 2 × the upper limit of normal (ULN)
e. Total bilirubin ≤ ULN, unless the subject has a known diagnosis of Gilbert’s syndrome
f. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN
g. Serum albumin ≥ 75% of the lower limit of normal
h. Lactate dehydrogenase ≤ 550 U/L
9. If with medical history of the following, eligibility should be discussed with the Medical Monitor:
a. 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)
b. Portal hypertension and/or hepatic vascular disorders
10. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned 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. |
|
| E.4 | Principal 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 mAb at any time, including JTX-4014; 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):
a. Biologic therapy
b. 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 EGFR 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:
a. 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
b. History of pneumonitis or interstitial lung disease
c. 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)
d. 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:
a. Brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
b. 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Mean percent change from baseline tumor size of all measurable existing and new lesions averaged over 9 and 18 weeks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study assessments and procedures will be performed as outlined in the Protocol Appendix 1 (Schedule of Assessments and Sampling Time Points for Cohort MC1) and Appendix 2 (Schedule of
Assessments and Sampling Time Points for Cohorts CC1 and CC2). |
|
| E.5.2 | Secondary end point(s) |
• ORR (percentage of subjects with CR + PR) according to RECIST, v1.1
• PFS according to RECIST, v1.1
• Landmark PFS rate at 9 months according to RECIST, v1.1
• Disease control rate (confirmed CR + confirmed PR + unconfirmed SD) according to RECIST, v1.1
• Duration of response in months according to RECIST, v1.1
• OS
• Incidence and grade of treatment-emergent adverse events (TEAEs)
• PK properties of JTX-4014 and vopratelimab
• Incidence of ADAs to either JTX-4014 or vopratelimab
• Incidence of neutralizing antibody (NAb) to either JTX-4014 or vopratelimab
• Association of baseline tumor RNA signature score with clinical outcomes |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study assessments and procedures will be performed as outlined in the Protocol Appendix 1 (Schedule of Assessments and Sampling Time Points for Cohort MC1) and Appendix 2 (Schedule of
Assessments and Sampling Time Points for Cohorts CC1 and CC2). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belarus |
| Bosnia and Herzegovina |
| Georgia |
| Moldova, Republic of |
| Russian Federation |
| Serbia |
| Turkey |
| Ukraine |
| Bulgaria |
| Croatia |
| Hungary |
| Latvia |
| Romania |
| Slovakia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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