A Phase 1/2 Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors
- Conditions
- Solid tumorsMedDRA version: 19.1 Level: LLT Classification code 10066438 Term: Anorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10030151 Term: Oesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.1 Level: LLT Classification code 10064444 Term: Invasive cervix cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and pTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001359-36-ES
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 815
1) Signed Written Informed Consent
2) Target Population
a) Subjects must have histologic or cytologic confirmation of a solid malignancy that is advanced (metastatic and/or unresectable)
b) Presence of at least 1 lesion with measurable disease as defined by RECIST v1.1 criteria for response assessment. Subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately. As of Protocol
Amendment 13, subjects undergoing biopsy do not need to have a biopsy lesion that is distinct from an index lesion.
c) Subjects must consent to allow the acquisition of existing FFPE material tissue block or tumor tissue sections for performance of correlative studies.
d) A minimum of 10 subjects each in the MEL cohort and the SCCHN cohort (the Dose Escalation and Cohort Expansion [Part 1; completed]) will be required to undergo mandatory pre-treatment and on-treatment biopsies in the cohort expansion phase at acceptable clinical risk as judged by the investigator. All other subjects will have the
option of undergoing pre-treatment, on-treatment, and post-treatment biopsies
e) The first dose of study drug must be at least 28 days from the last dose of prior therapy.
f) ECOG status of 0 or 1.
g) Life expectancy of = 12 weeks.
h) Adequate organ function for all subjects except those with HCC: see protocol
i) Adequate organ function for all HCC subjects: see protocol
j) Ability to comply with treatment, PK and pharmacodynamics sample collection and required study follow-up.
k) Subject re-enrollment: this study permits the re-enrollment of a subject who has discontinued the study as a pre-treatment failure (ie, subject has not been randomized/has not been treated). If re-enrolled, the subject must be re-consented.
l) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
m) Subjects must have resting baseline oxygen saturation measured by pulse oximetry of = 92% at rest on room air.
3) Age, Sex, and Reproductive Status
a) Men and women, ages = 18 years.
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study drug (ie, 30 days [duration of ovulatory cycle] plus the time required for the study drug to undergo approximately 5 half-lives.)
e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study drug (ie, 90 days [duration of sperm turnover] plus the time required for the study drug to undergo approximately 5 half-lives.)
f) Azoospermic ma
1) Target Disease Exceptions
a) Subjects with untreated CNS metastases
b) Participation in any prior study with ipilimumab/nivolumab, incl in comparator arms
c) SCCHN subjects only: Histologically confirmed recurrent/metastatic carcinoma of nasopharynx, and the skin and salivary gland/on-squamous histologies are not allowed
d) Subjects with carcinomatous meningitis
2) Medical History and Concurrent Diseases
a) Subjects with previous malignancies (except non-MEL skin cancers, and the following cancers: bladder, gastric, colon, esophageal endometrial, cervical/dysplasia, MEL, or breast) unless a complete remission was achieved at least 2 years prior to study entry + no additional therapy is required during the study period
b) Subjects with an active/known or suspected autoimmune disease
c) A known/underlying condition that, could make the administration of study drug hazardous, or could adversely affect the ability to comply with or tolerate drug. N/A from Prot Amdt 13 and next Amdts
d) Uncontrolled/significant cardiovascular disease
e) Known history of positive test for human immunodeficiency virus (HIV)/known acquired immunodeficiency syndrome. No HIV testing is required during screening. NOTE: Testing for HIV must be performed at study sites where mandated locally
i) Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. N/A from Prot Amdt 13 and next Amdts
ii) Subjects with a history of resolved hepatitis A virus infection are eligible. N/A from Prot 13 and next Amdts
f) Evidence of active infection = 7 days prior to initiation of study drug therapy. N/A from Prot Amdt 13 and next Amdts
g) Any serious/uncontrolled medical disorders
h) Any major surgery within 4 weeks of study drug administration
i) Subjects who are unable to undergo venipuncture and/or to tolerate venous access. N/A from Prot Amdt 13 and next Amdts
j) Any other sound medical, psychiatric and/or social reason determined by the investigator. N/A from Prot Amdt 13 and next Amdts
k) All toxicities attributed to systemic prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 or baseline before administration of study drug.
3) Prohibited Prior Treatments and/or Therapies
a) Prior treatment with an anti-KIR antibody/anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways except as noted below
b) Prior treatment regimens with any immune cell modulating antibody (anti-CD137 and anti-OX40). But, prior anti-CTLA-4 therapy is allowed if last dose is 101 days or more from the first dose. N/A from Prot Amdt 13 and next Amdts
c) Exposure to any other investigational drug within 4 weeks prior to the first dose
d) Treatment with any anti-cancer therapy, chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration
e) Prior focal palliative radiotherapy within 2 weeks prior to the first dose of study administration
f) Use of non-oncology v
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