Study of Cabozantinib as 2nd Line Treatment in Subjects With Locally Advanced or Metastatic Renal Cell Carcinoma (RCC) With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors (CaboPoint)

A Phase II, Multicentre, Open-label Study of Cabozantinib as 2nd Line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic Renal Cell Carcinoma With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors.

The overall objective of this study is to evaluate the efficacy and safety of cabozantinib as 2nd line treatment in subjects with unresectable, locally advanced or metastatic RCC with a clear-cell component, who progressed after prior Checkpoint Inhibitors (CPI) therapy with ipilimumab and nivolumab in combination or CPI combined with Vascular Endothelial Growth Factor (VEGF)-targeted therapy.

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Cabozantinib

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, A-5020
    • SALK - Salzburger Landesklinik
• France
  • Besançon, France, 25000
    • CHRU Besançon
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nancy, France, 54511
    • Institut de Cancérologie de Lorraine
  • Nîmes, France, 30029
    • CHU de NÎMES - Institut de Cancérologie du Gard
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Saint-Herblain, France, 44800
    • Institut de Cancérologie de l'Ouest
  • Strasbourg, France, 67091
    • CHU Strasbourg
  • Toulouse, France, 31059
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Berlin, Germany, D-10117
    • Universitätsmedzin Charité
  • Dresden, Germany, D-1307
    • University Hospital Carl Gustav Carus Dresden
  • Essen, Germany, D-45147
    • Universitätsklinikum Essen
  • Hamburg, Germany, d-20246
    • University Cancer Center Hamburg Eppendorf
  • Hanover, Germany, D-30625
    • Medizinische Hochschule Hannover
  • Jena, Germany, D-07747
    • Klinikum Der Friedrich-Schiller-Universitaet Jena
  • Lübeck, Germany, D-23538
    • Universitätsklinikum Schleswig-Holstein
  • Magdeburg, Germany, D-39120
    • Otto-von-Guericke-Universität University hospital Magdeburg
  • Münster, Germany, D-48149
    • University, Hospital Münster
  • Regensburg, Germany, D-93053
    • Caritas Krankenhaus St.Josef Klinik für Urologie
  • Tübingen, Germany, D-72076
    • University Hospital Tuebingen
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • The Netherlands Cancer Institute - Oncology
  • Eindhoven, Netherlands, 5604 DB
    • Máxima Medisch Centrum
  • Leiden, Netherlands, 2300-RC
    • Leiden University Medical Center
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Spain
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Lugo, Spain, 27003
    • Hospital Lucus Augusti
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28033
    • M.D. Anderson Center Madrid
• Switzerland
  • Bern, Switzerland, 3010
    • Universitätsspital Bern, Inselspital
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital - Edinburgh Cancer Centre
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital (RCH) - Sunrise Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All subjects must fulfil all the following criteria to be included in the study:

1. Subjects must provide a signed informed consent prior to any study-related procedures;
2. Male or female subjects must be aged ≥18 years on the day the informed consent is signed;
3. Subjects must have histologically confirmed unresectable, locally advanced (defined as disease not eligible for curative surgery or radiation therapy) or metastatic RCC with a clear-cell carcinoma component;
4. Subjects must have radiographic disease progression, according to Investigator's judgement following 1st line treatment with CPI (ipilimumab plus nivolumab) (Cohort A) or CPI in combination with VEGF-targeted therapy (Cohort B);
5. Subjects present ≥1 target lesion according to RECIST 1.1 per Investigator;
6. Subjects should have Eastern Cooperative Oncology Group (ECOG) status 0-1;
7. Subjects with treated brain metastases are eligible if metastases have been shown to be stable as per Investigator's judgement;

8. Subjects must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 15 days before baseline:

   1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
   2. Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
   3. Haemoglobin ≥ 9 g/dL (≥ 90 g/L).
   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal (ULN).
   5. Total bilirubin ≤ 1.5 × ULN. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L).
   6. Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation
   7. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine or 24-hour urine protein < 1 g.
9. Subject must have recovered to baseline or ≤ Grade 1 per CTCAE v5 from toxicities related to any prior treatments, unless Adverse Events (AE(s)) are clinically nonsignificant and/or stable on supportive therapy as determined by the Investigator;
10. Subject must have completed a steroid taper if he/she had an immune-related adverse event associated with immune CPI;
11. Female subjects of childbearing potential (i.e. less than or equal to 2 years postmenopause and not surgically sterile) must provide a negative pregnancy test within 7 days prior to the start of study treatment. If a urine test cannot be confirmed as negative, a negative serum pregnancy test is required;
12. Female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile) and their partners must agree to use highly effective methods of contraception that alone or in combination result in a failure rate of less than 1% per year when used consistently and correctly during the course of the study and for 4 months after the last dose of study treatment;
13. All male participants must agree to refrain from donating sperm and unprotected sexual intercourse with female partners during the study and for 120 days after the last dose of study treatment;
14. Subjects must be willing and able to comply with study requirements, remain at the investigational site for the required duration of each study visit and be willing to return to the investigational site for the follow up evaluation, as specified in the protocol
15. Subjects must be covered by social security or be the beneficiary of such a system (only applicable for French subjects).

Exclusion Criteria:

Subjects will not be included in the study if the subject:

1. Inability to swallow tablets;
2. Was treated with any other investigational medicinal product (IMP) within the last 30 days before baseline;
3. Was previously treated with cabozantinib;
4. Has a contraindication to Magnetic Resonance Imaging (MRI) or contrast medium used for Contrast Tomography (CT)-scan;
5. Presents untreated brain or leptomeningeal metastases, or current clinical or radiographic progression of known brain metastases;

6. Has a diagnosis of a serious cardiovascular disorder:

   1. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, or serious cardiac arrhythmias;
   2. Uncontrolled hypertension, defined as sustained blood pressure (BP) (>140 mm Hg systolic or >90 mm Hg diastolic pressure) despite optimal antihypertensive treatment;
   3. Stroke (including transient ischaemic attack (TIA)), myocardial infarction (MI) or other ischaemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before screening;
   4. History of risk factors for torsades de pointes (e.g., long QT syndrome);
7. Is receiving concomitant anticoagulation with coumarin agents (e.g. warfarin), direct thrombin inhibitor dabigatran, Direct Factor Xa inhibitors betrixaban or platelet inhibitors (e.g. clopidogrel); Note: The following are allowed anticoagulants: prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparin (LMWH) are permitted. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in patients without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before baseline without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumour.

8. Has a gastrointestinal (GI) disorder including those associated with a high risk of perforation or fistula formation:

   (a) Tumours invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction; b) Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before screening; Note: Complete healing of an intra-abdominal abscess must have been confirmed before screening

9. Presents a corrected QT (QTc) interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month prior to baseline; Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility

10. Presents clinically significant haematuria, hematemesis, or haemoptysis of >0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g.

    pulmonary haemorrhage) within 3 months before screening;

11. Presents cavitating pulmonary lesion(s) or known endobronchial disease manifestation;
12. Presents lesions invading major pulmonary blood vessels;

13. Has been diagnosed with other clinically significant disorders such as:

    1. Serious nonhealing wound/ulcer/bone fracture;
    2. Malabsorption syndrome;
    3. Uncompensated/symptomatic hypothyroidism;
    4. Moderate to severe hepatic impairment (Child-Pugh B or C);
    5. Requirement for haemodialysis or peritoneal dialysis;
    6. History of solid organ transplantation;
14. Has a predicted life expectancy of less than 3 months;
15. Has had prior surgery within 4 weeks prior to baseline. Note: If the subject has undergone major surgery, complete wound healing must have occurred 1 month prior to baseline
16. Has had palliative radiation therapy for bone within 2 weeks or for radiation fields including viscera within 4 weeks prior to baseline. Note: Resolution/healing of side effects must be complete prior to baseline;
17. Has a history of another active malignancy within 3 years from screening except for locally curable cancers that have been apparently cured, such as low-grade thyroid carcinoma, prostate cancer not requiring treatment (Gleason Grade ≤6), basal or squamous cell skin cancer, superficial bladder cancer, in situ melanoma, in situ prostate, cervix or breast carcinoma or other treated malignancies with <5% chance of relapse according to the Investigator;
18. Has a history of allergy to study treatment components or agents with a similar chemical structure or any excipient used in the formulation as listed in the Summary of Product Characteristics (SmPC) document;
19. Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded;
20. Has a serious medical or psychiatric condition that renders the subject unable to understand the nature, scope and possible consequences of the study, and/or presents an uncooperative attitude;
21. Is pregnant or breastfeeding. A β-human chorionic gonadotrophin (HCG) serum pregnancy test will be performed up to 7 days prior to baseline for all female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile);
22. Is likely to require treatment during the study with drugs that are not permitted by the study protocol;
23. Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the subject's safety

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Subjects who radiographically progressed after one prior line by CPI therapy with ipilimumab and nivolumab.	Drug: Cabozantinib; Oral tablets of 60mg, 40mg and 20 mg.; Other Names: Cabometyx
Experimental: Cohort B; Subjects who radiographically progressed after one prior line by CPI therapy combined with VEGF-targeted therapy.	Drug: Cabozantinib; Oral tablets of 60mg, 40mg and 20 mg.; Other Names: Cabometyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Objective Response Rate (ORR) Assessed by Independent Central Review	ORR was defined as the percentage of participants who achieved a partial response (PR) or complete response (CR) at any timepoint as determined by independent central review per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The confidence interval of the ORR was calculated using Clopper-Pearson exact method.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response (TTR) Assessed by Independent Central Review and Investigator	TTR was defined as the time from start of study treatment to the date of first evidence of response (PR or CR as determined by independent central review and Investigator per RECIST 1.1). The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Duration of Response (DOR) Assessed by Independent Central Review and Investigator	DOR was defined as the time from first documented response (PR or CR as determined by independent central review and Investigator per RECIST 1.1) to either disease progression (as determined by independent central review and Investigator per RECIST 1.1) or death due to any cause, whichever occurs first. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of ≥ 5 millimeters (mm). DOR was calculated using the Kaplan-Meier method.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Disease Control Rate (DCR) Assessed by Independent Central Review and Investigator	DCR was defined as the percentage of participants who achieved a PR, CR or stable disease (SD) as determined by independent central review and Investigator per RECIST 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. The PD was defined at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of ≥ 5 mm.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Progression-free Survival (PFS) Assessed by Independent Central Review and Investigator	PFS was defined as the time from start of study treatment to either disease progression (as determined by independent central review and Investigator per RECIST 1.1) or death due to any cause, whichever occurs first. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of ≥ 5 mm. PFS was calculated using the Kaplan-Meier method.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Cohort B: Objective Response Rate Assessed by Independent Central Review	ORR was defined as the percentage of participants who achieved a PR or CR at any timepoint as determined by independent central review per RECIST 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The CI of the ORR was calculated using Clopper-Pearson exact method.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Objective Response Rate Assessed by Investigator	ORR was defined as the percentage of participants who achieved a PR or CR at any timepoint as determined by Investigator per RECIST 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The CI of the ORR was calculated using Clopper-Pearson exact method.	Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months
Overall Survival (OS) Assessed by Investigator	OS was defined as the time from the start of treatment until death due to any cause. OS was calculated using the Kaplan-Meier method.	From the start of study treatment (Day 1) up to end of study, 45 months
Change From Baseline in Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-DRS) Score at Month 40	The FKSI-DRS questionnaire consisted of 9-items to evaluate participant's symptoms in the past 7 days such as lack of energy, pain, weight-loss, bone-pain, shortness of breath, fatigue, fever, blood in urine etc. Participants rated each question from 0 (not at all) to 4 (very much). Total score was calculated as the sum of the item responses divided by the number of items completed and multiplied by the total number of items in the scale. Total score ranged from 0 to 36. Higher scores indicated less symptoms. Baseline was defined as the last questionnaire answered prior to the first dose of study drug. A negative change from baseline indicated worse outcome.	Baseline (Day 1) and Month 40

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Publications and helpful links

General Publications

• Albiges L, Schmidinger M, Taguieva-Pioger N, Perol D, Grunwald V, Guemas E. CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma. Future Oncol. 2022 Mar;18(8):915-926. doi: 10.2217/fon-2021-1006. Epub 2021 Dec 16.

Helpful Links

• Lay language results summary

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): May 11, 2023
• Study Completion (Actual): February 12, 2026

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; cabozantinib
• Other Study ID Numbers: F-FR-60000-023; 2018-002820-18 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes