Efficacy and safety of Cabozantinib in patients with hepatocellular carcinoma progressing on or intolerant to prior treatment with immune checkpoint inhibitors: A phase II study (Immunocabo)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Humanitas Mirasole S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jan 2020 → 19 Jun 2025

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516972-14-00

EudraCT number

2019-002860-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To estimate in terms of PFS the efficacy of cabozantinib, given as second- or thirdline treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors.

Secondary objectives 2

1. To evaluate objective response rate (ORR) per RECIST 1.1, duration of response, time to treatment failure (TTF), time to progression (TTP), and OS (Overall Survival)..
2. To evaluate the safety and tolerability of cabozantinib in sequence after immunotherapy, according to NCI-CTCAE.

Conditions and MedDRA coding

Hepatocellular carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted)
2. A baseline tumor tissue (newly obtained) available at screening is optional. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines and requirements for such procedure. Biopsy cannot be performed less than ten days before treatment start.
3. The subject has disease that is not amenable to a locoregional treatment approach (eg, transplant, surgery, radiofrequency ablation, TACE)
4. Patients must have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic), the last of which includes immune checkpoint inhibitors. Alternatively, eligible patients may have experienced an immune-related, requiring treatment discontinuation.
5. Recovery to = Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically not significant and/or stable on supportive therapy
6. Age = 18 years old on the day of consent
7. ECOG performance status of 0 or 1
8. Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before treatment beginning: • absolute neutrophil count (ANC) = 1200/mm3 (= 1.2 x 109/L) • platelets = 60,000/mm3 (= 60 x 109/L) • hemoglobin = 8 g/dL (= 80 g/L)
9. Adequate renal function, based upon meeting the following laboratory criteria: serum creatinine = 1.5 × upper limit of normal or calculated creatinine clearance = 40 mL/min (using the Cockroft-Gault equation: (140 – age) x weight (kg)/(serum creatinine × 72 [mg/dL]) for males. (For females multiply by 0.85)
10. Child-Pugh Score of A
11. Total bilirubin = 2 mg/dL within 7 days before treatment start
12. Serum albumin = 2.8 g/dL (= 28 g/L) within 7 days before treatment start
13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5.0 upper limit of normal (ULN)
14. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
15. Capable of understanding and complying with the protocol requirements and signed informed consent
16. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
17. Female subjects of childbearing potential must not be pregnant at screening.

Exclusion criteria 12

1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
2. Child-Pugh score of B or C
3. Any type of anticancer agent (including investigational) within 2 weeks before treatment start Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of treatment start. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy
4. Prior cabozantinib treatment
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before treatment start. Eligible subjects must be without corticosteroid treatment at the time of treatment start
6. Concomitant anticoagulation, at therapeutic doses. Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (= 1 mg/day), and low-dose LMWH are permitted
7. Il paziente è affetto da patologie concomitanti non in fase di compenso: • Malattie cardiovascolari: cardiopatica congestizia sintomatica, sindrome anginosa, aritmie cardiache, ipertensione arteriosa non controllata, evento ischemico miocardico negli ultimi 6 mesi, evento tromboembolico negli ultimi 3 mesi (i pazienti con trombosi delle vene porta/epatiche sono includibili) • Malattie gastrointestinali con elevato rischio di perforazione o formazione di fistole: tumore che infiltra il tratto gastrointestinale, ulcera peptica attiva, malattie infiammatorie dell’intestino, diverticolite, colecistite, colangite sintomatica, appendicite, pancreatite acuta, ostruzione acuta dei dotti pancreaticobiliari, ostruzione alte vie digestive, fistola addominale, perforazione gastrointestinale, ostruzione intestinale, ascesso intraddominale negli ultimi 6 mesi (conferma della completa risoluzione dell’ascesso prima dell’avvio del trattamento)
8. Major surgery within 2 months before treatment start. Complete healing from major surgery must have occurred 1 month before treatment start. Complete healing from minor surgery (eg, tooth extraction) must have occurred at least 7 days before treatment start.
9. Cavitating pulmonary lesion(s) or endobronchial disease
10. Lesion invading a major blood vessel including, but not limited to: inferior vena cava, pulmonary artery, or aorta. Subjects with lesions invading the portal vasculature are eligible
11. Clinically significant bleeding risk including the following within 3 months of treatment start
12. Other clinically significant disorders such as: Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV), or known acquired immunodeficiency syndrome (AIDS)-related illness. Subjects with active hepatitis virus infection controlled with antiviral therapy are eligible Serious non-healing wound/ulcer/bone fracture Malabsorption syndrome Uncompensated/symptomatic hypothyroidism Requirement for hemodialysis or peritoneal dialysis History of solid organ transplantation Rare hereditary problems of galactose intolerance. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible Moderate or severe ascites Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms. Inability to swallow tablets Previously identified allergy or hypersensitivity to components of the study treatment formulations Pregnant or lactating females Diagnosis of another malignancy within 2 years before treatment start, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS on cabozantinib treatment (considering as PFS events: clinical or radiological progressive disease, per RECIST 1.1, or death).

Secondary endpoints 2

1. Objective Response Rate (ORR) as per RECIST 1.1, duration of response, Treatment Time Failure (TTF), Time to Progression (TTP), and Overall Survival (OS).
2. To evaluate the safety and tolerability, according to NCI-CTCAE v.5

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Humanitas Mirasole S.p.A.

Sponsor organisation

Humanitas Mirasole S.p.A.

Address

Via Alessandro Manzoni 56

City

Rozzano

Postcode

20089

Country

Italy

Scientific contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Prof. Lorenza Rimassa

Public contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Prof. Lorenza Rimassa

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications