Advanced Solid Tumor, Gynecologic Cancer
Conditions
Keywords
lucitanib, nivolumab, antineoplastic agents immunological, antineoplastic agents, tyrosine kinase inhibitors, gynecologic neoplasms, checkpoint inhibitor, ovarian cancer, fallopian tube cancer, primary peritoneal cancer, endometrial cancer, clear cell cancer, cervical cancer, PD-1 inhibitor, Immuno-oncology
Brief summary
This is an open-label, Phase 1b/2 study to determine the recommended dose of lucitanib in combination with nivolumab in patients with an advanced solid tumor (Phase 1b); followed by evaluation of the safety and efficacy of lucitanib and nivolumab in patients with an advanced gynecological solid tumor (Phase 2) and evaluate the effects of dosing under fasting or fed state (Food Effect)
Interventions
DRUGLucitanib
Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg.
DRUGNivolumab
IV nivolumab 480 mg will be administered once every 4 weeks.
Sponsors
Bristol-Myers Squibb
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Clovis Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * ≥ 18 years of age * Adequate organ function * Life expectancy ≥ 3 months * Women of childbearing potential must have a negative serum pregnancy test * Advanced/metastatic solid tumor (Phase 1b) * Availability of tumor tissue at screening * ECOG performance status of 0 to 1 * Measurable disease (RECIST v1.1) (Phase 2) * Advanced, recurrent, or metastatic gynecological solid tumor (Phase 2) * Willing and able to fast, and to eat a high-fat breakfast (Food Effect) General
Exclusion criteria
* Prior treatment with lucitanib * Active second malignancy * Active central nervous system brain metastases * Pre-existing duodenal stent or any gastrointestinal disorder * Known history of HIV or AIDs; positive result of hepatitis B or C viruses * Evidence of interstitial lung disease, active pneumonitis, myocarditis, or history of myocarditis * Active, known or suspected autoimmune disease (eg, autoimmune hepatitis) * Condition requiring systemic treatment with corticosteroids or other immune suppressive medications * Unstable or uncontrolled hypertension (BP ≥ 140/90 mmHg) * Prior treatment with a VEGFR-tyrosine kinase inhibitor (Phase 2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b) | First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years) | Incidence of adverse events and clinical lab abnormalities defined as dose-limiting toxicities and maximum tolerated dose. |
| Best Overall Response Rate (Phase 2) | From first dose of study drug until disease progression (up to approximately 2 years) | Confirmed best overall response (PR or CR) based on investigator assessment of objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) | Area under the curve \[AUCss\] |
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2] | From Cycle 2 to Cycle 5 (each cycle is 28 days) | Minimum plasma concentration \[Cmin,ss\] |
| Acute and long-term safety and tolerability of the combination (Phase 2) | From first dose of study drug until disease progression (up to approximately 2 years) | Incidence of AEs, clinical lab abnormalities, and dose modifications. |
| The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] | From first dose of study drug to Day -1 | Area under the curve \[AUC\] |
| Lucitanib PK Profile at single dose [Food Effect Cohort] | From first dose of study drug to Day -1 | Area under the curve \[AUC\] |
| Further evaluation of preliminary efficacy of combination (Phase 2) | From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years) | Duration of response, progression-free survival, and disease control per RECIST v1.1, overall survival. |
Countries
Austria, Belgium, Germany, Italy, Spain, United States
Outcome results
None listed