A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Advanced Solid Tumor, Gynecologic Cancer

Intervention / Treatment
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* Drug: Lucitanib
* Drug: Lucitanib
* Drug: Lucitanib
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b: Dose Escalation<br>- Up to 50 patients with advanced solid tumor | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|
| Experimental: Phase 1b: Food Effect Cohort<br>- Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|
| Experimental: Phase 2: Expansion Cohort - Endometrial Cancer<br>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 | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Subjects will be allowed to intrapatient dose escalate in increments of 2 mg up to a total dose of 10 mg QD lucitanib if they meet the study specific clinical criteria.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|
| Experimental: Phase 2: Expansion Cohort - Ovarian Cancer<br>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 | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Subjects will be allowed to intrapatient dose escalate in increments of 2 mg up to a total dose of 10 mg QD lucitanib if they meet the study specific clinical criteria.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|
| Experimental: Phase 2: Expansion Cohort - Clear Cell Cancer<br>Recurrent, metastatic clear cell carcinoma of ovarian, fallopian tube, primary peritoneal or endometrial origin At least 1 prior platinum- and taxane-based chemotherapy regimen | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Subjects will be allowed to intrapatient dose escalate in increments of 2 mg up to a total dose of 10 mg QD lucitanib if they meet the study specific clinical criteria.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|
| Experimental: Phase 2: Expansion Cohort - Cervical Cancer<br>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 | Drug: Lucitanib<br>* Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Subjects will be allowed to intrapatient dose escalate in increments of 2 mg up to a total dose of 10 mg QD lucitanib if they meet the study specific clinical criteria.<br>* Other names: CO-3810;Drug: Nivolumab<br>* IV nivolumab 480 mg will be administered once every 4 weeks.<br>* Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b) | Incidence of adverse events and clinical lab abnormalities defined as dose-limiting toxicities and maximum tolerated dose. | First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years) | 
| Best Overall Response Rate (Phase 2) | 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. | From first dose of study drug until disease progression (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and long-term safety and tolerability of the combination (Phase 2) | Incidence of AEs, clinical lab abnormalities, and dose modifications. | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Further evaluation of preliminary efficacy of combination (Phase 2) | Duration of response, progression-free survival, and disease control per RECIST v1.1, overall survival. | From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years) | 
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] | Area under the curve [AUCss] | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) | 
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] | Maximum plasma concentration [Cmax,ss] | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) | 
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect] | Total clearance of drug after oral administration [CLss/F] | From first dose of study drug to the end of Cycle 1 (each cycle is 28 days) | 
| Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2] | Minimum plasma concentration [Cmin,ss] | From Cycle 2 to Cycle 5 (each cycle is 28 days) | 
| Lucitanib PK Profile at single dose [Food Effect Cohort] | Area under the curve [AUC] | From first dose of study drug to Day -1 | 
| Lucitanib PK Profile at single dose [Food Effect Cohort] | Maximum plasma concentration [Cmax] | From first dose of study drug to Day -1 | 
| Lucitanib PK Profile at single dose [Food Effect Cohort] | Time to maximum plasma concentration [Tmax] | From first dose of study drug to Day -1 | 
| The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] | Area under the curve [AUC] | From first dose of study drug to Day -1 | 
| The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] | Maximum plasma concentration [Cmax] | From first dose of study drug to Day -1 | 
| The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] | Time to maximum plasma concentration [Tmax] | From first dose of study drug to Day -1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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