Description:
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)
Title
- Brief Title: A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor
- Official Title: LIO-1: A Phase 1b/2, Open-Label Study to Evaluate the Safety and Efficacy of Lucitanib in Combination With Nivolumab in Patients With An Advanced, Metastatic Solid Tumor
Clinical Trial IDs
- ORG STUDY ID:
CO-3810-101
- SECONDARY ID:
ENGOT-GYN3/AGO/LIO
- NCT ID:
NCT04042116
Conditions
- Advanced Solid Tumor
- Gynecologic Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Lucitanib | CO-3810 | Phase 1b: Dose Escalation |
| Lucitanib | CO-3810 | Phase 1b: Food Effect Cohort |
| Lucitanib | CO-3810 | Phase 2: Expansion Cohort - Cervical Cancer |
| Nivolumab | Opdivo, BMS-936558 | Phase 1b: Dose Escalation |
Purpose
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)
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1b: Dose Escalation | Experimental | - Up to 50 patients with advanced solid tumor | |
| Phase 1b: Food Effect Cohort | Experimental | - Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled | |
| Phase 2: Expansion Cohort - Endometrial Cancer | Experimental | Recurrent endometrial carcinoma at least 1 prior platinum-based chemotherapy regimen
Up to 10 patients who have progressed on treatment with 1 prior PD-(L)1 inhibitor administered as monotherapy will be allowed to enroll | |
| Phase 2: Expansion Cohort - Ovarian Cancer | Experimental | Recurrent high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, of any histology excluding clear cell carcinoma
At least 2 prior chemotherapy regimens which at least 1 must have been platinum-doublet chemotherapy
Up to 10 subjects with recurrent ovarian, fallopian tube, or primary peritoneal cancer, of any histology excluding clear cell carcinoma who have progressed within 6 months after completing first-line platinum-based chemotherapy will be allowed to enroll | |
| Phase 2: Expansion Cohort - Clear Cell Cancer | Experimental | Recurrent, metastatic clear cell carcinoma of ovarian, fallopian tube, primary peritoneal or endometrial origin
At least 1 prior platinum- and taxane-based chemotherapy regimen | |
| Phase 2: Expansion Cohort - Cervical Cancer | Experimental | Persistent or recurrent cervix cancer of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma histology
At least 1 prior regimen of platinum-based chemotherapy, with or without bevacizumab, for metastatic disease | |
Eligibility 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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b) |
| Time Frame: | First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Incidence of adverse events and clinical lab abnormalities defined as dose-limiting toxicities and maximum tolerated dose. |
Secondary Outcome Measures
| Measure: | Acute and long-term safety and tolerability of the combination (Phase 2) |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Incidence of AEs, clinical lab abnormalities, and dose modifications. |
| Measure: | Further evaluation of preliminary efficacy of combination (Phase 2) |
| Time Frame: | From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Duration of response, progression-free survival, and disease control per RECIST v1.1, overall survival. |
| Measure: | Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] |
| Time Frame: | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | Area under the curve [AUCss] |
| Measure: | Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] |
| Time Frame: | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | Maximum plasma concentration [Cmax,ss] |
| Measure: | Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] |
| Time Frame: | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | Total clearance of drug after oral administration [CLss/F] |
| Measure: | Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2] |
| Time Frame: | From Cycle 2 to Cycle 5 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | Minimum plasma concentration [Cmin,ss] |
| Measure: | Lucitanib PK Profile at single dose [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Area under the curve [AUC] |
| Measure: | Lucitanib PK Profile at single dose [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Maximum plasma concentration [Cmax] |
| Measure: | Lucitanib PK Profile at single dose [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Time to maximum plasma concentration [Tmax] |
| Measure: | The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Area under the curve [AUC] |
| Measure: | The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Maximum plasma concentration [Cmax] |
| Measure: | The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] |
| Time Frame: | From first dose of study drug to Day -1 |
| Safety Issue: | |
| Description: | Time to maximum plasma concentration [Tmax] |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Clovis Oncology, Inc. |
Trial 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
Last Updated
August 30, 2021
