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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

Tracking Information
First Submitted Date  ICMJE August 24, 2017
First Posted Date  ICMJE August 30, 2017
Last Update Posted Date June 19, 2019
Actual Study Start Date  ICMJE September 19, 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
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 2 months of treatment, whichever occurs first ]
The incidence of Grade 3 or 4 adverse events (AEs) related to CAN04 administration and according to the National Cancer Institute - Common Terminology Criteria for Ad-verse Events (CTCAE, version 4.03).
Change History Complete list of historical versions of study NCT03267316 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • Maximum concentration (Cmax) [ Time Frame: 5 weeks ]
    Maximum plasma concentration of CAN04
  • Terminal half-life (t1/2) [ Time Frame: 5 weeks ]
    Terminal half-life of CAN04
  • Clearance (CL) [ Time Frame: 5 weeks ]
    Plasma clearance of CAN04
  • Apparent volume of distribution during the terminal phase (VZ) [ Time Frame: 5 weeks ]
    Apparent volume of distribution of CAN04 during the terminal phase
  • 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
  • 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.
  • Preliminary signs of efficacy as assessed by tumor response [ Time Frame: One year ]
    Tumor response (irRC).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
  • Maximum concentration (Cmax) [ Time Frame: 5 weeks ]
    Maximum plasma concentration of CAN04
  • Terminal half-life (t1/2) [ Time Frame: 5 weeks ]
    Terminal half-life of CAN04
  • Clearance (CL) [ Time Frame: 5 weeks ]
    Plasma clearance of CAN04
  • Apparent volume of distribution during the terminal phase (VZ) [ Time Frame: 5 weeks ]
    Apparent volume of distribution of CAN04 during the terminal phase
  • 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
  • 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.
  • Preliminary signs of efficacy as assessed by tumor response [ Time Frame: One year ]
    Tumor response.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Non Small Cell Lung Cancer
  • Pancreatic Ductal Adenocarcinoma
  • Triple Negative Breast Cancer
  • Colorectal Cancer
Intervention  ICMJE
  • 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
  • Drug: Nab-paclitaxel
    Standard of care treatment
Study Arms  ICMJE
  • 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]
    Intervention: Biological: CAN04
  • Experimental: Monotherapy (Q1W)
    Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W).
    Intervention: Biological: CAN04
  • 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).
    Intervention: Biological: CAN04
  • 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).
    Interventions:
    • Biological: CAN04
    • Drug: Cisplatin
    • Drug: Gemcitabine
  • 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).
    Interventions:
    • Biological: CAN04
    • Drug: Gemcitabine
    • Drug: Nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 8, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2017)
65
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lars Thorsson, PhD +46 46 275 62 60 lars.thorsson@cantargia.com
Contact: Susanne Magnusson, PhD
Listed Location Countries  ICMJE Austria,   Belgium,   Denmark,   Germany,   Netherlands,   Norway,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03267316
Other Study ID Numbers  ICMJE CAN04CLIN001
2017-001111-36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cantargia AB
Study Sponsor  ICMJE Cantargia AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ahmad Awada, Professor Jules Bordet Institute, Brussels, Belgium
PRS Account Cantargia AB
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP