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

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ClinicalTrials.gov Identifier: NCT03267316
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Cantargia AB

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. In addition, early signs of efficacy during treatment with CAN04 will be investigated.


Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Pancreatic Ductal Adenocarcinoma Triple Negative Breast Cancer Colorectal Cancer Biological: CAN04 Drug: Cisplatin Drug: Gemcitabine Drug: Nab-paclitaxel Phase 1 Phase 2

Detailed Description:

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 at the RP2D level. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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 four 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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Dose Escalation Followed by Dose Expansion, Safety and Tolerability Trial of CAN04, a Fully Humanized Monoclonal Antibody Against IL1RAP, in Subjects With Solid Malignant Tumors
Actual Study Start Date : September 19, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


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
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




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 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 ]
    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).


Secondary Outcome Measures :
  1. Maximum concentration (Cmax) [ Time Frame: 5 weeks ]
    Maximum plasma concentration of CAN04

  2. Terminal half-life (t1/2) [ Time Frame: 5 weeks ]
    Terminal half-life of CAN04

  3. Clearance (CL) [ Time Frame: 5 weeks ]
    Plasma clearance of CAN04

  4. Apparent volume of distribution during the terminal phase (VZ) [ Time Frame: 5 weeks ]
    Apparent volume of distribution of CAN04 during the terminal phase

  5. Area under the curve from time 0 to infinity (AUC0-∞) [ Time Frame: 5 weeks ]
    Area under the plasma concentration curve from time 0 to infinity

  6. Anti-drug antibodies (ADA) against CAN04 [ Time Frame: Through study completion, an average of 6 months ]
    Immunogenicity of CAN04 after repeated administrations, assessed by ADA titers in serum.

  7. Preliminary signs of efficacy as assessed by tumor response [ Time Frame: One year ]
    Tumor response (irRC).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 year.
  2. Measurable disease in accordance to immune related Response Criteria (irRC) by computed tomography (CT) or magnetic resonance imaging (MRI) scan, no more than 6 weeks prior to screening.
  3. At least 4 weeks since the last dose of chemotherapy, 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.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  5. Histologically or cytologically confirmed, unresectable, locally advanced or metastatic NSCLC, PDAC, CRC or TNBC tumor, relapsed or refractory to standard therapy or for which there is no standard therapy (applicable for Part I only)
  6. Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic squamous or non-squamous NSCLC or PDAC, relapsed or refractory to standard of care therapy or for whom there is no standard therapy (applicable for Part II, monotherapy arms only).
  7. Histologically or cytologically confirmed diagnosis of unresectable stage IIIB or stage IV squamous or non-squamous NSCLC (applicable Part II, Combination - NSCLC arm only)
  8. Newly diagnosed, treatment naїve, histologically confirmed, unresectable, locally advanced or metastatic (stage III or stage IV) PDAC (applicable Part II, Combination - PDAC arm only).

Exclusion Criteria:

  1. 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.
  2. Clinical evidence of an active second malignancy.
  3. Subjects with a life expectancy <12 weeks.
  4. Uncontrolled or significant cardiovascular disease defined as New York Heart Association Classification III, or IV.
  5. Immunocompromised subject currently receiving systemic therapy.
  6. Other medical conditions that in the opinion of the investigator disqualify the subject for inclusion.
  7. Applicable Part II, Combination - NSCLC arm only

    1. Prior lines of treatment with anti-cancer medication other than pembrolizumab administered as 1st line.
    2. Known tumor EGFR mutation, unless contraindication to EGFR-directed therapy.
    3. Known tumor ALK rearrangements, unless contraindication to ALK-directed therapy or ALK-directed therapy not available.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267316


Contacts
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Contact: Lars Thorsson, PhD +46 46 275 62 60 lars.thorsson@cantargia.com
Contact: Susanne Magnusson, PhD

Locations
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Austria
Landeskrankenhaus Salzburg Recruiting
Salzburg, Austria, 5020
Contact: Richard Greil, Prof, Dr.    +43 57 255 25800    r.greil@salk.at   
Medizinische Universität Wien Recruiting
Vienna, Austria, A-1090
Contact: Sabine Zöchbauer-Müller, MD, PhD    +43 140 400 44290    sabine.zoechbauer-mueller@meduniwien.ac.at   
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Contact: Christiane Jungels, Dr    +32 2 541 7342    christiane.jungels@bordet.be   
CHU de Liège Not yet recruiting
Liège, Belgium, B-4000
Contact: Joelle Collignon, MD    32 4 366 82 50    joelle.collignon@chuliege.be   
Denmark
Rigshospitalet, Department of Oncology Recruiting
Copenhagen, Denmark, 2100
Contact: Ulrik Lassen, Prof, MD,PhD    +45 354 58 923    Ulrik.Lassen@regionh.dk   
Herlev og Gentofte Hospital Recruiting
Herlev, Denmark, 2730
Contact: Rikke Eefsen, MD, PhD    +45 38 68 9381    rikke.helene.loevendahl.eefsen@regionh.dk   
Odense University Hospital Recruiting
Odense, Denmark, 5000
Contact: Per Pfeiffer, Prof. Dr.    +45 65 41 15 90    per.pfeiffer@rsyd.dk   
Germany
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Sebastian Ochsenreither, PD Dr. med.    +49 30 450 564 960    sebastian.ochsenreither@charite.de   
Asklepios Klinik Altona Not yet recruiting
Hamburg, Germany, 227 63
Contact: Dirk Arnold, Prof. Dr. med.    +49 40 1818 81 1210    d.arnold@asklepios.com   
Netherlands
Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Neeltje Steeghs, MD, PhD    +31 20 512 9111    n.steeghs@nki.nl   
Erasmus University Medical Center, Department of Medical Oncology Recruiting
Rotterdam, Netherlands, 3015 CE
Contact: Ferry ALM Eskens, MD, PhD    +31 10 703 48 97    f.eskens@erasmusmc.nl   
Norway
Oslo University Hospital, Radiumhospitalet Recruiting
Oslo, Norway, 0379
Contact: Tormod Kyrre Guren, Dr.    +47 2 541 3188    uxtour@ous-hf.no   
Sweden
Karolinska University Hospital Recruiting
Stockholm, Sweden, 171 64
Contact: Jeffrey Yachnin, MD, PhD    +46 85 177 3193    jeffrey.yachnin@sll.se   
Sponsors and Collaborators
Cantargia AB
Investigators
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Principal Investigator: Ahmad Awada, Professor Jules Bordet Institute, Brussels, Belgium

Additional Information:
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Responsible Party: Cantargia AB
ClinicalTrials.gov Identifier: NCT03267316     History of Changes
Other Study ID Numbers: CAN04CLIN001
2017-001111-36 ( EudraCT Number )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cantargia AB:
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

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Adenocarcinoma
Triple Negative Breast Neoplasms
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Cisplatin
Gemcitabine