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

Colorectal Cancer Clinical Trial

— CANFOUR  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03267316
• Other study ID #: CAN04CLIN001
• Secondary ID: 2017-001111-36
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 19, 2017
• Est. completion date: December 31, 2023

Study information

• Verified date: October 2023
• Source: Cantargia AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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]

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 167
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 year.

2. Measurable disease in accordance to iRECIST 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 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 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.

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 na?ve, 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.

Exclusion Criteria:

1. Subjects receiving live vaccination, etanercept or other TNF-a 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 metastatic 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 (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.

Related Conditions & MeSH terms

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

Intervention

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
• Gemcitabine
Standard of care treatment
• Nab-paclitaxel
Standard of care treatment
• Carboplatin
Standard of care treatment
• Pemetrexed
Standard of care treatment

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Medizinische Universität Wien	Vienna
Belgium	Institut Jules Bordet	Brussels
Belgium	University Hospital Gasthuisberg	Leuven
Belgium	CHU de Liège	Liège
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet, Department of Oncology	Copenhagen
Denmark	Herlev og Gentofte Hospital	Herlev
Denmark	Odense University Hospital	Odense
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Asklepios Klinik Altona	Hamburg
Germany	Universitätsklinikum Ulm	Ulm
Latvia	Pauls Stradinš Clinical University Hospital	Riga
Latvia	Riga East Clinical University Hospital	Riga
Lithuania	The Hospital of Lithuanian University of Health Sciences	Kaunas
Lithuania	National Cancer Institute	Vilnius
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	Erasmus University Medical Center, Department of Medical Oncology	Rotterdam
Norway	Oslo University Hospital, Radiumhospitalet	Oslo
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Sweden	Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Cantargia AB

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Estonia,  Germany,  Latvia,  Lithuania,  Netherlands,  Norway,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maximum concentration (Cmax)	Maximum plasma concentration of CAN04	5 weeks
Secondary	Terminal half-life (t1/2)	Terminal half-life of CAN04	5 weeks
Secondary	Clearance (CL)	Plasma clearance of CAN04	5 weeks
Secondary	Apparent volume of distribution during the terminal phase (VZ)	Apparent volume of distribution of CAN04 during the terminal phase	5 weeks
Secondary	Area under the curve from time 0 to infinity (AUC0-8)	Area under the plasma concentration curve from time 0 to infinity	5 weeks
Secondary	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
Secondary	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

External Links

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