A First-in-Human Study Of CAN04 In Patients With Solid Malignant Tumors

Study Overview

A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors

This study will evaluate the safety, tolerability, and preliminary antitumor activity of CAN04 both as a monotherapy and in combination with standard of care treatment in subjects with solid cancer tumors. Following completion of the first part, the dose escalation cohorts, and determination of maximum tolerated dose or recommended phase 2 dose (MTD/RP2D), safety and tolerability will be further evaluated in an expanded cohort of subjects with pancreatic or lung cancer, as monotherapy or in combination with the standard of care treatment and to identify the RP2D of CAN04 in combination with standard of care. In addition, early signs of efficacy during treatment with CAN04 will be investigated.

CAN04 is a first-in-class fully humanized and ADCC enhanced monoclonal antibody, targeting the Interleukin 1 Receptor Accessory Protein (IL1RAP). The CAN04 strategy is to attack the IL1RAP target molecule using an effective antibody-based cancer treatment. In preclinical (in vitro and in vivo) studies, CAN04 has shown two distinct mechanisms of action: 1. By blocking the intracellular signals from the IL1RAP target molecule, thereby impairing the cancer cells' ability to secrete tumor stimulating cytokines, in turn reducing tumor inflammation and tumor progression. 2. Through antibody dependent cellular cytotoxicity (ADCC) against IL1RAP expressing tumor cells where CAN04 stimulates natural killer (NK) cells to attack the tumor cells. The study is a combined phase 1/2a, open-label, dose-escalation followed by dose expansion, safety and tolerability clinical trial, in patients with relapsed or refractory solid tumors. It consists of two parts. In Part I (Dose Escalation - DE), the intention is to include patients with any of the four solid tumor types: Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). In this part of the study safety and tolerability will be documented and the MTD/ RP2D will be determined. Patients will stay on CAN04 treatment until disease progression, unacceptable toxicity, or discontinuation for any other reason. [Completed December 2018] In Part II (Expansion Cohort - EC), safety and tolerability will be further evaluated in an expanded cohort of subjects with PDAC or NSCLC to identify RP2D of CAN04 in combination with standard of care. In addition, early signs of efficacy during treatment with CAN04 will be investigated, as monotherapy or in combination with the standard of care. Patients will stay on treatment until disease progression, unacceptable toxicity, or discontinuation for any other reason. [Enrollment to all arms completed]

Non Small Cell Lung Cancer
Pancreatic Ductal Adenocarcinoma
Triple Negative Breast Cancer
Colorectal Cancer

BIOLOGICAL: CAN04
DRUG: Cisplatin
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
DRUG: Carboplatin
DRUG: Pemetrexed

CAN04CLIN001
2017-001111-36 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-08-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-08-21
First Submitted that Met QC Criteria 2017-08-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-08-22
First Posted (ACTUAL) 2017-08-30	Results First Posted N/A	Last Verified 2024-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose escalation Cohorts of 3 subjects will receive once weekly (Q1W) treatment with CAN04. The Dose Limiting Toxicity (DLT) observation period for each dose level will be the first 21 days of treatment with CAN04. [Completed December 2018]	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.
EXPERIMENTAL: Monotherapy (Q1W) Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W).	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.
EXPERIMENTAL: Monotherapy (Q1W/Q2W) Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W).	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.
EXPERIMENTAL: Combination - NSCLC (NCG) Subjects with NSCLC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (cisplatin/gemcitabine).	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion. DRUG: Cisplatin Standard of care treatment DRUG: Gemcitabine Standard of care treatment
EXPERIMENTAL: Combination - PDAC Subjects with PDAC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine).	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion. DRUG: Gemcitabine Standard of care treatment DRUG: Nab-paclitaxel Standard of care treatment
EXPERIMENTAL: Combination - PDAC (1 mg/kg) Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion. DRUG: Gemcitabine Standard of care treatment DRUG: Nab-paclitaxel Standard of care treatment
EXPERIMENTAL: Combination - PDAC (2,5 mg/kg) Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion. DRUG: Gemcitabine Standard of care treatment DRUG: Nab-paclitaxel Standard of care treatment
EXPERIMENTAL: Combination - non-squamous NSCLC (NCP) Subjects with non-squamous NSCLC will receive CAN04 on Day 1 and 8 in cycles of 21 days in combination with standard-of-care therapy (carboplatin/pemetrexed).	BIOLOGICAL: CAN04 A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion. DRUG: Carboplatin Standard of care treatment DRUG: Pemetrexed Standard of care treatment

Primary Outcome Measures	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	The incidence of Grade 3 or higher adverse events (AEs) related to CAN04 administration and according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE, version 4.03).	From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever occurs first

Secondary Outcome Measures	Measure Description	Time Frame
Maximum concentration (Cmax)	Maximum plasma concentration of CAN04	5 weeks
Terminal half-life (t1/2)	Terminal half-life of CAN04	5 weeks
Clearance (CL)	Plasma clearance of CAN04	5 weeks
Apparent volume of distribution during the terminal phase (VZ)	Apparent volume of distribution of CAN04 during the terminal phase	5 weeks
Area under the curve from time 0 to infinity (AUC0-∞)	Area under the plasma concentration curve from time 0 to infinity	5 weeks
Anti-drug antibodies (ADA) against CAN04	Immunogenicity of CAN04 after repeated administrations, assessed by ADA titers in serum.	Through study completion, an average of 6 months
Preliminary signs of efficacy as assessed by tumor response	Tumor response (irRC Part I Part II Monotherapy arms; iRECIST Part II Combination arms)	One year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Subjects must be eligible to receive first line standard chemotherapy regimen with cisplatin/gemcitabine or a second line standard chemotherapy regimen with cisplatin/gemcitabine after relapsing from first line with pembrolizumab monotherapy.
Subjects with actionable mutations (EGFR, ALK, ROS) can be enrolled if they have previously progressed to all approved standard of care targeted therapies and the next line of standard therapy is a platinum doublet. 6. Histologically or cytologically confirmed diagnosis of unresectable stage III or stage IV non-squamous NSCLC (applicable Part II, Combination - non-squamous NSCLC NCP arm only).

Subjects must be eligible to receive first line standard chemotherapy regimen with carboplatin/pemetrexed or a second line standard chemotherapy regimen with carboplatin/pemetrexed after relapsing from first line with pembrolizumab monotherapy.
Subjects with actionable mutations (EGFR, ALK, ROS) can be enrolled if they have previously progressed to all approved standard of care targeted therapies and the next line of standard therapy is a platinum doublet. 7. Newly diagnosed, treatment naїve, histologically confirmed, unresectable, locally advanced or metastatic (stage III or stage IV) PDAC (applicable Part II, Combination - PDAC arms only).

Subjects must be eligible to receive treatment with nab-paclitaxel and gemcitabine.

Prior lines of treatment with anti-cancer medication other than pembrolizumab administered as 1st line.
Known tumor EGFR mutation, unless contraindication to EGFR-directed therapy or if the subject has progressed to all approved anti-EGFR therapies.
Known tumor ALK rearrangements, unless contraindication to ALK-directed therapy or ALK-directed therapy not available or if the subject has progressed to all approved anti-EGFR therapies.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Ahmad Awada, Professor, Jules Bordet Institute, Brussels, Belgium

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Paulus A, Zemaitis M, Cicenas S, Zvirbule Z, Sanfridson A, Millrud CR, Magnusson S, Losic N, Tersago D, Garcia-Ribas I, Thorsson L, Paz-Ares LG. Safety, efficacy, and analysis of biomarkers in patients with advanced non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab (CAN04) in combination with platinum doublet. Lung Cancer. 2025 Aug;206:108664. doi: 10.1016/j.lungcan.2025.108664. Epub 2025 Jul 14.
Robbrecht D, Jungels C, Sorensen MM, Spanggaard I, Eskens F, Fretland SO, Guren TK, Aftimos P, Liberg D, Svedman C, Thorsson L, Steeghs N, Awada A. First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours. Br J Cancer. 2022 Apr;126(7):1010-1017. doi: 10.1038/s41416-021-01657-7. Epub 2021 Dec 13.

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