| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Stage Solid Tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced Stage Solid Tumors |
|
| 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 | LLT |
| E.1.2 | Classification code | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 identify the recommended Phase 2 dose(s) (RP2D[s]) for JNJ-63723283 (Part 1)
• To assess the anti-tumor activity of JNJ-63723283 at the RP2D(s) in subjects with selected advanced cancers including non-small cell lung cancer (NSCLC), melanoma, renal, bladder, small cell lung cancer (SCLC), and gastric/esophageal cancer and high-level microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) (Part 2) |
|
| E.2.2 | Secondary objectives of the trial |
• To characterize the safety of JNJ-63723283 in subjects with advanced solid tumors
• To characterize the pharmacokinetics of JNJ-63723283 administered intravenously or subcutaneously
• To assess the immunogenicity of JNJ-63723283
• To assess the clinical activity of JNJ-63723283 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥ 18 years of age
2. Have evaluable disease,
2a. For Part 2, at least 1 measurable lesion that can be accurately assessed at baseline by CT (or magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per RECIST v1.1
3.1. Criterion modified per Amendment 2
3.2. Criterion modified per Amendment 3
3.3. Type of cancer:
Part 1 of the study:
Has any type of advanced or refractory solid tumor malignancy, except lymphoma, that is metastatic or unresectable and previously received or was ineligible for standard treatment options including appropriate molecularly
targeted therapies (eg, subjects with epidermal growth factor receptor [EGFR] mutant NSCLC or with NSCLC with anaplastic lymphoma tyrosine kinase [ALK] rearrangement).
Part 2 of the study:
Histologically or cytologically confirmed diagnosis of 1 of the following unresectable Stage III or IV solid tumor malignancies and previously received or was ineligible for standard treatment options including appropriate molecularly targeted therapies (eg, subjects with EGFR mutant NSCLC or with NSCLC with ALK rearrangement):
• NSCLC
- PD-L1-high tumor sample (≥50% tumor cells stained positive for PDL1) by a PD-L1 immunohistochemistry (IHC) test performed by a local laboratory or by the central laboratory designated by the sponsor
NOTE: Subjects with EGFR mutant or other molecular aberration who progress on appropriate molecular targeted therapy do not require prior treatment with platinum-containing chemotherapy.
• Bladder cancer (urothelial carcinoma)
• Renal cell carcinoma
• Gastric/esophageal carcinoma
• Melanoma
• SCLC
• MSI-H or dMMR CRC
- MSI-H or dMMR by a polymerase chain reaction (PCR), next generation sequencing, or IHC test performed by a local laboratory or by the central laboratory designated by the sponsor Progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
• Thymoma, including thymic carcinoma
4. Have an Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1 (Attachment 1)
5.1. Criterion modified per Amendment 2
5.2. Have organ and bone marrow function as follows without blood product support: see table protocol page 44
6. Criterion modified per Amendment 2
6.1. Has thyroid function laboratory values within normal range. Note: If
thyroid stimulating hormone (TSH) is not within normal limits, the subject may still be eligible if T3 (either total or free) and free T4 are within normal limits.
7. Women of childbearing potential must have a negative serum pregnancy test at Screening using highly sensitive pregnancy test.
8. Willing to use contraceptive methods consistent with local regulations for subjects participating in clinical studies during and after the study until 5 months after the last dose of study drug.
a. Women of childbearing potential must agree to use 2 highly effective methods of contraception consistent with local regulations (<1% per year failure rate when used consistently and correctly).
b. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
c. Women and men must agree not to donate sperm or eggs (ova, oocytes), respectively, during the study and after the study until 5 months after the last dose of study drug.
9. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
10. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the subject’s disease.
11. Subjects enrolled into Part 2 must have tumor tissue available for correlative studies. Fresh tumor biopsy is preferred. Archival tissue must meet the following criteria: archival sections within 4 months of sectioning that have been stored at 2° to 8° C in the dark or archival tumor blocks within 5 years of collection. Subjects without tissues meeting the aforementioned archived tissue criteria must undergo a fresh biopsy. |
|
| E.4 | Principal exclusion criteria |
1. Has uncontrolled intercurrent illness, including but not limited to ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure (New York Heart Association class III-IV; Attachment 2), unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that would limited compliance with study requirements
2. Has had prior treatment with an anti-PD-1 antibody, anti-PD-L1 antibody or anti-PD-L2 antibody
3. Treatment with any local or systemic anti-neoplastic therapy, radiotherapy (excluding limited palliative radiation), or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, up to a maximum wash-out period of 28 days prior to the initiation of study drug administration.
4. Criterion modified per Amendment 2
4.1. Has brain or leptomeningeal metastases unless asymptomatic, have been treated, have been stable for >4 weeks as documented by radiographic imaging with no evidence of cavitation or hemorrhage in the brain lesion, and do not require prolonged (>2 weeks) systemic corticosteroid therapy. Subjects are not permitted to receive enzymeinducing antiepileptic drugs.
5. Has not recovered (ie, ≤Grade 1 or baseline) from AEs except alopecia, peripheral neuropathy related to prior anticancer therapy and stable anemia (ie, untransfused Hb ≥8.5 g/dL without the need for supportive transfusion within 2 weeks of screening) at the time of treatment allocation
6. Criterion modified per Amendment 2
6.1. Has an active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents. Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement will not be excluded from the study. Subjects with a history of transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent (eg, acute Lyme arthritis) will not be excluded from the study.
7. Grade 3 or higher toxicity effects from previous treatment with immunotherapy
8. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia), or to JNJ-63723283 excipients (refer to Investigator's Brochure)
9. Has taken immunosuppressive doses of systemic medications, such as corticosteroids (doses >10 mg/day prednisone or equivalent), within 2 weeks before the planned first dose of study drug
10. A woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 5 months after the last dose of study drug
11. A man who plans to father a child while enrolled in this study or within 5 months after the last dose of study drug.
12. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
13. Had major surgery (eg, requiring general anesthesia) within 4 weeks before dosing, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 4 weeks after the last dose of study drug administration.
14. Criterion modified per Amendment 2
14.1. Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) positivity at screening. If positive, further testing of quantitative levels to rule out active infection is required.
15. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
16. Criterion modified per Amendment 2
16.1. Vaccinated with a live vaccine within 28 days prior to the first dose of study drug. Annual inactivated influenza vaccine is permitted. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Frequency and severity of dose-limiting toxicity (DLT)
• Overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in subjects with selected advanced solid tumors |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
- The DLT evaluation period is defined as 2 weeks from the start of the first JNJ-63723283 infusion.
- Every 8 weeks (+/-2 weeks window) until Week 24 then every 12 weeks (+/-2 weeks window) relative to the date of first dose, and regardless of dose or schedule |
|
| E.5.2 | Secondary end point(s) |
• Safety profile of JNJ-63723283 (safety parameters include but are not limited to the frequency and severity of adverse events [AEs] and immune-related AEs [irAEs], vital signs measurements, clinical laboratory values, and electrocardiograms [ECGs])
• Serum JNJ-63723283 pharmacokinetic parameters including but not limited to maximum observed serum concentration (Cmax), area under the concentration-time curve between 2 defined sampling points, t1 and t2 (AUCt1-t2), half-life (T1/2), total systemic clearance of drug after IV administration (CL), volume of distribution at steady-state (Vss), and accumulation ratio (R)
• Presence of anti-JNJ-63723283 antibodies and effect on serum JNJ-63723283 concentrations
• ORR per the Immune-Related Response Criteria (irRC), duration of response (DOR), clinical benefit rate (CBR) and progression-free survival (PFS) by both RECIST v.1.1 and irRC, and OS |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- The Safety profile of JNJ-63723283 will be evaluated throughout the whole study
- Serum pharmacokinetic parameters defined above will be evaluated throughout the whole study
- The presence of anti-JNJ-63723283 antibodies and effect on serum concentrations will be evaluated throughout the whole study
- OSS, DOR, PFS and OS will be evaluated at the end of the study |
|
| 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 | No |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
Immunogenicity
Biomarker
Exploratory |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | No |
| E.8.1.1 | Randomised | No |
| 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 | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| 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 |
| Italy |
| Poland |
| Russian Federation |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| The end of the study is defined as last study assessment for the last subject on study or anytime the sponsor terminates the study, whichever comes first. |
|
| 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 | 4 |
| 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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