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

Sponsor

Clovis Oncology, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04042116

Collaborator

Bristol-Myers Squibb (Industry), European Network of Gynaecological Oncological Trial Groups (ENGOT) (Other)

227

Enrollment

Locations

Arms

53.1

Anticipated Duration (Months)

8.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Gynecologic Cancer	Drug: Lucitanib Drug: Lucitanib Drug: Lucitanib Drug: Nivolumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

227 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 29, 2019

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b: Dose Escalation - Up to 50 patients with advanced solid tumor	Drug: Lucitanib Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558
Experimental: Phase 1b: Food Effect Cohort - Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled	Drug: Lucitanib Oral lucitanib will be administered once daily (QD). The dose will be 6 mg. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558
Experimental: Phase 2: Expansion Cohort - Endometrial Cancer 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 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. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558
Experimental: Phase 2: Expansion Cohort - Ovarian Cancer 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 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. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558
Experimental: Phase 2: Expansion Cohort - Clear Cell Cancer 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 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. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558
Experimental: Phase 2: Expansion Cohort - Cervical Cancer 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 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. Other Names: CO-3810 Drug: Nivolumab IV nivolumab 480 mg will be administered once every 4 weeks. Other Names: Opdivo BMS-936558

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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] [From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)]
Maximum plasma concentration [Cmax,ss]
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)]
Total clearance of drug after oral administration [CLss/F]
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]
Lucitanib PK Profile at single dose [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]
Maximum plasma concentration [Cmax]
Lucitanib PK Profile at single dose [Food Effect Cohort] [From first dose of study drug to Day -1]
Time to maximum plasma concentration [Tmax]
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]
The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] [From first dose of study drug to Day -1]
Maximum plasma concentration [Cmax]
The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] [From first dose of study drug to Day -1]
Time to maximum plasma concentration [Tmax]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
2	UC San Diego Moores Cancer Center	San Diego	California	United States	92093
3	Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
4	Florida Cancer Specialists	Sarasota	Florida	United States	34232
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	NYU Langone Laura and Isaac Perlmutter Cancer Center	New York	New York	United States	10016
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Duke University School of Medicine	Durham	North Carolina	United States	27710
9	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
10	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
11	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
12	Tennessee Oncology	Nashville	Tennessee	United States	37203
13	Swedish Cancer Institute	Seattle	Washington	United States	98107
14	Medical University of Innsbruck	Innsbruck		Austria	6020
15	Saint Luc Univerisity Hospital	Brussels		Belgium	1200
16	University Hospital Ghent	Ghent		Belgium	9000
17	University Hospitals Leuven, Campus Gasthuisberg	Leuven		Belgium	3000
18	University Hospital Carl Gustav Carus	Dresden		Germany	01307
19	Kliniken Essen-Mitte	Essen		Germany	45136
20	University Hospital Mannhein	Mannheim		Germany	68167
21	Polyclinic S. Orsola-Malpighi	Bologna		Italy	40138
22	National Cancer Institute -IRCCS "Fondazione G. Pascale	Naples		Italy	80131
23	Foundation IRCCS Hospital Agostino Gemelli	Rome		Italy	00168
24	University Hospital Reina Sofia	Cordoba	Andalusia	Spain	14004
25	University Hospital Vall d'Hebron	Barcelona		Spain	08035
26	Navarra University Clinic	Madrid		Spain	28027
27	La Paz University Hospital	Madrid		Spain	28046

Sponsors and Collaborators

Clovis Oncology, Inc.
Bristol-Myers Squibb
European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators

Principal Investigator: Erika Hamilton, MD, Tennessee Oncology, PLLC
Principal Investigator: Nicole Concin, MD, KEM Kliniken Essen Mitte Evang. Huyssens-Stiftung