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

NCT03267316 | Completed Phase 1

• 2 other identifiers: CAN04CLIN0012017-001111-36
• Study Type: interventional
• Target: 167
• Locations: 10 countries
• Sites: 22

Brief Summary

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.

Conditions

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

Keywords

First-in-Human; Phase 1; Phase 2; Antibody, Monoclonal; IL1RAP; Safety; Tolerability; Cancer; Solid tumor; Malignant; Dose escalation; Dose expansion; CAN04; Immunoglobulin; Clinical Trial; Infusion; Antineoplastic; Anticancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Maximum concentration (Cmax)

  5 weeks

• Terminal half-life (t1/2)

  5 weeks

• Clearance (CL)

  5 weeks

• Apparent volume of distribution during the terminal phase (VZ)

  5 weeks

• Area under the curve from time 0 to infinity (AUC0-∞)

  5 weeks

Study Arms (8)

Dose escalation

EXPERIMENTAL

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

Monotherapy (Q1W)

EXPERIMENTAL

Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W).

Biological: CAN04

Monotherapy (Q1W/Q2W)

EXPERIMENTAL

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

Combination - NSCLC (NCG)

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Gemcitabine

Combination - PDAC

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Nab-paclitaxel

Combination - PDAC (1 mg/kg)

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Nab-paclitaxel

Combination - PDAC (2,5 mg/kg)

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Nab-paclitaxel

Combination - non-squamous NSCLC (NCP)

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Pemetrexed

Interventions

CAN04 BIOLOGICAL

A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.

Combination - NSCLC (NCG); Combination - PDAC; Combination - PDAC (1 mg/kg); Combination - PDAC (2,5 mg/kg); Combination - non-squamous NSCLC (NCP); Dose escalation; Monotherapy (Q1W); Monotherapy (Q1W/Q2W)

Cisplatin DRUG

Standard of care treatment

Combination - NSCLC (NCG)

Gemcitabine DRUG

Standard of care treatment

Combination - NSCLC (NCG); Combination - PDAC; Combination - PDAC (1 mg/kg); Combination - PDAC (2,5 mg/kg)

Nab-paclitaxel DRUG

Standard of care treatment

Combination - PDAC; Combination - PDAC (1 mg/kg); Combination - PDAC (2,5 mg/kg)

Carboplatin DRUG

Standard of care treatment

Combination - non-squamous NSCLC (NCP)

Pemetrexed DRUG

Standard of care treatment

Combination - non-squamous NSCLC (NCP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 year.
• Measurable disease in accordance to iRECIST by computed tomography (CT) or magnetic resonance imaging (MRI) scan, no more than 6 weeks prior to screening.
• At least 4 weeks since the last dose of radiation therapy, immunotherapy, or surgery; at least 6 weeks for therapy which is known to have delayed toxicity; at least 4 weeks since treatment with biologic/targeted therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Histologically or cytologically confirmed diagnosis of unresectable stage III or stage IV squamous or non-squamous NSCLC (applicable Part II, Combination - NSCLC (NCG) arm only).
• 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.
• 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.
• 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.

You may not qualify if:

• Subjects receiving live vaccination, etanercept or other TNF-α inhibitors or any other investigational agents during or just prior to (within 28 days of first study drug administration) participation in this study.
• Clinical evidence of an active metastatic second malignancy.
• Subjects with a life expectancy \<12 weeks.
• Uncontrolled or significant cardiovascular disease defined as New York Heart Association Classification III, or IV.
• Immunocompromised subject currently receiving systemic therapy.
• Applicable Part II, Combination - NSCLC (NCG and NCP) arms only
• 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.

Sponsors & Collaborators

• Cantargia AB: lead

Study Sites (25)

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Medizinische Universität Wien

Vienna, A-1090, Austria

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

University Hospital Gasthuisberg

Leuven, 3000, Belgium

Location

CHU de Liège

Liège, B-4000, Belgium

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Rigshospitalet, Department of Oncology

Copenhagen, 2100, Denmark

Location

Herlev og Gentofte Hospital

Herlev, 2730, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

East Tallinn Central Hospital

Tallinn, 11312, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Asklepios Klinik Altona

Hamburg, 227 63, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Pauls Stradiņš Clinical University Hospital

Riga, 1002, Latvia

Location

Riga East Clinical University Hospital

Riga, 1079, Latvia

Location

The Hospital of Lithuanian University of Health Sciences

Kaunas, 50161, Lithuania

Location

National Cancer Institute

Vilnius, 08660, Lithuania

Location

Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

Erasmus University Medical Center, Department of Medical Oncology

Rotterdam, 3015 CE, Netherlands

Location

Oslo University Hospital, Radiumhospitalet

Oslo, 0379, Norway

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Quirónsalud Madrid

Madrid, 28223, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Karolinska University Hospital

Stockholm, 171 64, Sweden

Location

Related Publications (2)

• 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.

  PMID: 40680438 DERIVED

• 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.

  PMID: 34903842 DERIVED

Related Links

• Poster presentation at ESMO 2018
• Oral presentation at ASCO annual meeting 2019
• Poster presentation at ESMO 2021
• Poster presentation at ASCO annual meeting 2022
• Poster presentation at ASCO annual meeting 2022
• Poster presentation at AACR annual meeting 2023
• Poster presentation at ASCO annual meeting 2023

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Colorectal Neoplasms; Neoplasms

Interventions

Cisplatin; Gemcitabine; 130-nm albumin-bound paclitaxel; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ahmad Awada, Professor

  Jules Bordet Institute, Brussels, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part I of the study is designed to define the Maximum Tolerated Dose/ Recommended Phase 2 Dose (MTD/RP2D) of CAN04 in subjects with relapsed or refractory Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). \[Completed December 2018\] Part II consists of seven treatment arms and aims to establish the safety and tolerability of CAN04 as monotherapy and in combination with the standard of care in subjects with NSCLC or PDAC, as well as to investigate early signs of efficacy \[Enrollment to all arms completed\].

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 30, 2017
• Study Start: September 19, 2017
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

ES (2); BE (3); LA (2); DE (3); DK (4); LI (2); NL (2); SE (1); AU (2); NO (1)