A first-in-human study to evaluate the clinical activity of JNJ-63723283 in patients with advanced cancers.

Phase 1

• Conditions: Advanced Stage Solid Tumors; MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002017-22-PL
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-21
• Last Update Posted: 21 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 215

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
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 repres

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified