A first-in-human study to evaluate the clinical activity of JNJ-63723283 in patients with advanced cancers.
- Conditions
- Advanced Stage Solid TumorsMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002017-22-GB
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 215
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 acce
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 t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method