| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Stage Solid Tumors |
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| E.1.1.1 | Medical condition in easily understood language |
| Advanced Stage Solid Tumors |
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| 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 |
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| 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 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 NSCLC, melanoma, renal, bladder, SCLC, gastric/esophageal cancer, and MSI-H or dMMR CRC (Part 2)
•To determine a SC RP2D as defined by a dose regimen for JNJ-63723283 SC delivery which achieves similar exposure as with JNJ-63723283 IV delivery at the RP2Ds for IV administration (Part 3 and Part 4)
•To evaluate PK non-inferiority of JNJ-63723283 SC administration compared to JNJ-63723283 IV administration of JNJ-63723283 monotherapy (Part 5)
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| E.2.2 | Secondary objectives of the trial |
• To characterize the safety of JNJ-63723283 in subjects with advanced solid tumors by IV and by SC delivery
• To characterize the pharmacokinetics of JNJ-63723283 administered IV or SC
• To assess the immunogenicity of JNJ-63723283
• To assess the clinical activity of JNJ-63723283
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥ 18 years of age
2.1 Have evaluable disease; For Part 5, at least 1 measurable lesion that can be accurately assessed at baseline by CT and is suitable for repeated assessment as per RECIST version 1.1
3. Criterion modified per Amendment 3
3.5. Type of cancer:
Part 1 - 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.
Part 2 - 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: NSCLC, Bladder cancer, Renal cell carcinoma, Gastric/esophageal carcinoma, Melanoma, SCLC, MSI-H or dMMR CRC.
Part 3 and Part 4 - 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 .
Part 5 - Has a histologically or cytologically confirmed diagnosis of unresectable Stage III or Stage IV cutaneous or mucosal melanoma. Individuals with uveal or ocular melanoma are excluded.
4. Have an Eastern Cooperative Oncology Group performance status 0 or 1
5.3. Have organ and bone marrow function as follows without blood product support:
-Hemoglobin - ≥8.5 g/dL
-ANC≥1.5 x 10^9/L
-Platelets ≥ 75.0 x 10^9/L
-AST and ALT≤3 x ULN (or ≤4 x ULN for subjects with tumor involvement in the liver)
-Total bilirubin≤1.5 x ULN
-Serum creatinine≤1.5 x ULN or a calculated GFR ≥50 mL/min/1.73mm^2 . Part 5 - calculated GFR ≥50 mL/min
-Left ventricular ejection fraction - Within normal institutional limits
-Corrected QT interval (QTcF or QTcB) ≤ 480 msec based on the average of triplicate assessments performed 5 (±3) minutes apart
6.1. Has thyroid function laboratory values within normal range.
7.1 Females of childbearing potential must have a negative serum pregnancy test at Screening using highly sensitive pregnancy test.
8.1 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. Female 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 male subject 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. Female and male subjects 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.
12. In Part 5, up to 1 line of prior therapy for melanoma is allowed with the exception of prior anti-PD-1 antibody, anti-PD-L1 antibody, or anti-PD-L2 antibody therapy.
13. Human immunodeficiency virus-positive participants are eligible if they meet all of the following:
a. No detectable viral load at screening
b. CD4+ count >300 cells/mm^3 at screening
c. No acquired immunodeficiency syndrome -defining opportunistic infections within 6 months of screening.
d. Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.
14. Subjects enrolled into Part 5 must have tumor tissue available for central determination of PDL1 status. The exception is participants who do not have sufficient tissue available for central testing, in which case a Sponsor-approved local assay may be accepted. |
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| 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.
4.2. 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.
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
10.1 A female 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
11.1 A male 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
16.2. Vaccinated with a live vaccine within 28 days prior to the first dose of study drug. COVID-19 vaccination with mRNA or replication incompetent viral vector vaccines and annual inactivated influenza vaccines are permitted. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1 Frequency and severity of dose-limiting toxicity (DLT)
2 Overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in subjects with selected advanced solid tumors
3 JNJ-63723283 PK parameters after 1st dose administration as observed in Part 3 and JNJ-63723283 PK parameters after 4th dose as observed during every 3-week (Q3W) dosing in Part 4
4 Average concentration in Cycle 1 and concentration observed at the last timepoint prior to dosing at steady state
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|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 The DLT evaluation period is defined as 2 weeks from the start of the first JNJ-63723283 infusion.
2 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
3 After 1st dose administration in Part 3 and after 4th dose as observed during every 3-week (Q3W) dosing in Part 4
4 Pre-dose of Dose 7 |
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| E.5.2 | Secondary end point(s) |
1 Safety profile of JNJ-63723283 (safety parameters include but are not limited to the frequency and severity of AEs and irAEs, vital signs measurements, clinical laboratory values, and electrocardiograms [ECGs])
2 Serum JNJ-63723283 IV PK parameters including but not limited to Cmax, AUC between 2 defined sampling points, t1 and t2 (AUCt1-t2), T1/2, CL, Vss, and accumulation ratio (R)
3 C(max), AUC(0-6 weeks), AUC(0-infinity) (if applicable), T1/2 (if applicable), after JNJ-63723283 600 mg first SC dose administration (Part 3)
4 C(max), AUC(0-3 weeks) post 4th dose, concentration observed at the last timepoint prior to dosing (Ctrough) just prior to administration of the 2nd, 3rd, 4th and 5th dose with JNJ-63723283 SC delivery (Part 3 and Part 4)
5 Presence of anti-JNJ-63723283 antibodies and effect on serum JNJ-63723283 concentrations
6 ORR per the irRC, duration of response (DOR), CBR, and PFS by both RECIST version 1.1 and irRC, and OS
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 The Safety profile of JNJ-63723283 will be evaluated throughout the whole study
2 Serum pharmacokinetic parameters defined above will be evaluated throughout the whole study
3 After JNJ-63723283 600 mg first SC dose administration (Part 3)
4 post 4th dose and prior to administration of the 2nd, 3rd, 4th and 5th dose with JNJ 63723283 SC delivery (Part 3 and Part 4)
5 The presence of anti-JNJ-63723283 antibodies and effect on serum concentrations will be evaluated throughout the whole study
6 OSS, DOR, PFS and OS will be evaluated at the end of the study |
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| 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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 41 |
| 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 |
| Argentina |
| Brazil |
| China |
| India |
| Korea, Republic of |
| Mexico |
| Thailand |
| United States |
| Poland |
| Bulgaria |
| Spain |
| Germany |
| Italy |
| Moldova, Republic of |
| Russian Federation |
| Turkey |
| United Kingdom |
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| 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. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 27 |
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