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

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

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)

Study Overview

• Status: Suspended
• Conditions: Gynecologic Cancer; Advanced Solid Tumor
• Intervention / Treatment: Drug: Lucitanib; Drug: Lucitanib; Drug: Lucitanib; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Anticipated): 227
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / 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: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo
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) at the starting dose of 6 mg.; Other Names: CO-3810; Drug: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo
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.; Other Names: CO-3810; Drug: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo
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.; Other Names: CO-3810; Drug: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo
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.; Other Names: CO-3810; Drug: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo
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.; Other Names: CO-3810; Drug: Lucitanib; Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.; Other Names: CO-3810; 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: BMS-936558; Opdivo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Clovis Oncology, Inc.
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: endometrial cancer; ovarian cancer; fallopian tube cancer; primary peritoneal cancer; nivolumab; checkpoint inhibitor; PD-1 inhibitor; cervical cancer; Immuno-oncology; antineoplastic agents; tyrosine kinase inhibitors; lucitanib; antineoplastic agents immunological; gynecologic neoplasms; clear cell cancer
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CO-3810-101; ENGOT-GYN3/AGO/LIO (Other Identifier: ENGOT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

• IPD Sharing Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
• IPD Sharing Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No