A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors

NCT05116891 | Completed Phase 1 DMC

• 1 other identifier: CAN04CLIN004
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a Phase 1/2, open-label, multicentric, non-randomised, parallel-arm study that aims to establish the safety, tolerability, and initial efficacy of CAN04 in combination with 3 SoC chemotherapies (mFOLFOX, DTX, and G/C).

Conditions

Advanced Solid Tumors; Colorectal Cancer; Non Small Cell Lung Cancer; Biliary Tract Cancer

Keywords

Nadunolimab; CAN04; CRC; NSCLC

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of CAN04 in combination with selected standard hemotherapy regimens and to establish MTD and/or RP2D.

  Frequency, duration, and severity of AEs

  Until 30 days after the last dose of study treatment (EOT visit) in Phase 1

• To assess the preliminary efficacy of CAN04 in combination with chemotherapy regimens measured as tumour response.

  ORR defined as the percentage of subjects with PR or CR based on RECIST v1.1.

  Until approximately 3 years after last treatment in Phase 2.

Secondary Outcomes (5)

• To assess preliminary anti-tumour activity of CAN04 in combination with selected standard chemotherapy regimens.

  Every 12 weeks until disease progression or death from any cause in Phase 1.

• To assess preliminary anti-tumour activity of CAN04 in combination with selected standard chemotherapy regimens.

  Until approximately 3 years after last treatment in Phase 2.

• To further characterise the safety and tolerability of CAN04 in combination with chemotherapy at the MTD/RP2D.

  Until 30 days after the last dose of study treatment (EOT visit) in Phase 2.

• To assess preliminary anti-tumour activity of CAN04 in combination with selected standard chemotherapy regimens.

  Until 30 days after the last dose of study treatment (EOT visit).

• To assess PK of CAN04 after a single dose and at steady state

  From first dose until 30 days after the last dose of study treatment (EOT visit)

Other Outcomes (7)

• To evaluate the effect of CAN04 when administered in combination with chemotherapy on subject-reported cancer-related fatigue.

  Until 30 days after the last dose of study treatment (EOT visit) in Phase 2

• To evaluate the effect of CAN04 when administered in combination with chemotherapy on health-related quality of life.

  Until 30 days after the last dose of study treatment (EOT visit) in Phase 2

• To assess changes in serum biomarker IL-6 when CAN04 is administered in combination with standard of care chemotherapy.

  From first dose until 30 days after the last dose of study treatment (EOT visit).

Study Arms (3)

CAN04 and chemotherapy (mFOLFOX)

EXPERIMENTAL

12 cycles for mFOLFOX/CAN04-Each cycle is 2 weeks.mFOLFOX/CAN04 treatment arm: CAN04 and mFOLFOX are administered on Day 1 with a mFOLFOX continuation of regime on Day 2. CAN04 is only administered on Day 1.

Drug: CAN04 (nadunolimab); Drug: mFOLFOX

CAN04 and chemotherapy (DTX)

EXPERIMENTAL

6 cycles for DTX/CAN04, Cycles are 3 weeks. DTX/CAN04 treatment arm: CAN04 and DTX are administered on Day 1 followed by CAN04 in monotherapy on Day 8.

Drug: CAN04 (nadunolimab); Drug: DTX

CAN04 and chemotherapy (G/C)

EXPERIMENTAL

8 cycles for G/C/CAN04, Cycles are 3 weeks. G/C/CAN04 treatment arm: CAN04 and G/C are administered on Day 1/Day 8.

Drug: CAN04 (nadunolimab); Drug: G/C

Interventions

CAN04 (nadunolimab) DRUG

FULLY HUMANISED MONOCLONAL ANTIBODY AGAINST IL1RAP

Also known as: nadumolimab

CAN04 and chemotherapy (DTX); CAN04 and chemotherapy (G/C); CAN04 and chemotherapy (mFOLFOX)

mFOLFOX DRUG

mFOLFOX/CAN04

Also known as: Modified Folfox; Oxaliplatin, 5-fluorouracil (5-FU), leucovorin

CAN04 and chemotherapy (mFOLFOX)

DTX DRUG

DTX/CAN04

Also known as: Docetaxel

CAN04 and chemotherapy (DTX)

G/C DRUG

G/C/CAN04

Also known as: Gemcitabine and cisplatin

CAN04 and chemotherapy (G/C)

Eligibility Criteria

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

You may qualify if:

• PHASE 1 and PHASE 2:
• Subject must be able to understand and sign written informed consent, according to local guidelines.
• Subject must be ≥18 years of age at the time of signature of the ICF.
• Subject must have an ECOG PS score of 0 or 1.
• Subject must have adequate organ function, as indicated by the laboratory values in the protocol
• Women of childbearing potential must have a negative serum pregnancy test before study entry. Women of non-childbearing potential will have had at least 24 continuous months of natural (spontaneous) amenorrhea, and an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms), or have had hysterectomy, bilateral salpingectomy or bilateral oophorectomy\>6 weeks before screening.
• Male or female subjects: Male subjects with female partners of childbearing potential and female subjects of childbearing potential are required to use 2 forms of acceptable contraception, including 1 barrier method, during their participation in the study and for 4 months after the last dose of CAN04 or for 6 months after the last dose of the relevant chemotherapies, whatever is longer. Male subjects must also refrain from donating sperm during their participation in the study and in the period when contraceptives are required
• Subjects must not have contraindications according to the approved local summary of product characteristics (SmPC) for the respective components of the SoC chemotherapies.
• PHASE 1 (Dose Escalation)
• Subject has histologically or cytologically confirmed diagnosis of locally advanced cancer or metastatic cancer. Subjects do not need to have measurable disease per response evaluation criteria in solid tumours (RECIST) v1.1.
• Subject has a condition where all standard therapeutic options with proven survival benefit have been exhausted, refused by the subject, or are contraindicated. OR Subject has a condition where 1 of the 3 study regimens (mFOLFOX, DTX, or G/C) is considered SoC for the next-line treatment.
• Subject has additional disease characteristics per treatment arm:
• mFOLFOX Arm: All subjects eligible for mFOLFOX can be enrolled. A maximum of 2 previous lines of cytotoxic chemotherapy treatment for metastatic disease is allowed (targeted agents without cytotoxic effect will not be counted).
• DTX Arm: Subjects eligible to receive DTX as monotherapy for NSCLC can be enrolled in this treatment arm. No more than 2 lines of prior systemic anti-cancer therapies for the metastatic disease are allowed. Targeted therapy is not counted as prior therapy. Subjects who received DTX monotherapy in a prior line of therapy are not eligible.
• G/C Arm: All subjects eligible for G/C can be enrolled (including first-line treatments).. Subjects with BTC will be prioritized.

You may not qualify if:

• Subject has a known or suspected allergy to study drugs (including chemotherapy regimens), any of its components.
• Subject has uncontrolled or significant heart failure defined as New York Heart Association Classification III or IV.
• Subjects to receive mFOLFOX or DTX: having peripheral sensory neuropathy Grade ≥2.
• Subject has QT interval corrected using Fridericia's formula (QTcF) \>480 msec at screening.
• Subjects to receive DTX and CAN04: if they have liver metastases and aspartate aminotransferase (AST) and/or ALT \>1.5 × upper limit of normal (ULN) concomitant with alkaline phosphatase \>2.5 × ULN.
• Subject has uncontrolled brain metastases. Subjects are allowed to be enrolled if brain metastasis has been previously treated with surgery, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of prednisone or equivalent) at the time of the first dose of CAN04. For asymptomatic subjects, without known brain metastases, brain imaging during screening is not required. Subjects with known brain metastases should have undergone brain imaging in the frame of the imaging screening procedures.
• Subject has an active severe infection requiring parenteral antibiotics at the time of enrolment or subjects currently receiving oral antibiotics as a continuation of a previous course of parenteral antibiotics. Subjects can be enrolled when antibiotic treatment is complete and if there are no signs of residual infection. Note: Subjects with BTC who required stent placement should have the procedure completed 2 weeks before and be free of antibiotics (oral or parenteral) for at least 1 week before first treatment administration.
• Subject has a history of a relevant autoimmune disease as per assessment of the investigator or autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses \>10 mg/day).
• Subject is expected to require any other form of systemic or localised anti-neoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
• Subject has had an allogeneic tissue/solid organ transplant.
• Subject received a live vaccination, etanercept, or other tumour necrosis factor-alpha inhibitors prior to (within 28 days of first study drug administration) participation in this study. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, a wash-out of 2 weeks before first administration of study drug is recommended.
• Subject had treatment with systemic anti-cancer treatments, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Subjects should have recovered from previous treatment toxicity to Grade 1, baseline (except alopecia and peripheral neuropathy).
• Subject received radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for palliative irradiation to peripheral tumour lesions, other than for example spine or pelvis, without increased risk for delayed cytopenias) and has not recovered to Grade 1 or better from related toxicity of such therapy (except for alopecia).
• Subject has known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. Note: Subjects who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be included but must have an undetectable hepatitis B viral load.
• Subjects who test positive for human immunodeficiency virus (HIV) are NOT excluded from this study but must meet the following criteria:

Sponsors & Collaborators

• Cantargia AB: lead

Study Sites (6)

EDOG Institut de Cancerologie de l'Ouest - PPDS

Saint-Herblain, Boulevard Jacques Monod, 44805, France

Location

Centre Georges François Leclerc

Dijon, Côte-d'Or, 21079, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Biliary Tract Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Docetaxel; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Ignacio Garcia-Ribas, MD, PhD

  Cantargia AB

  STUDY DIRECTOR

Study Design

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

Model Details: Dose Escalation Phase (Phase 1): mFOLFOX and Gemcitabine/Cisplatin Arm: Subjects with any type of locally advanced or metastatic cancer who have no therapeutic alternatives with proven survival benefit or who are eligible for mFOLFOX or gemcitabine/cisplatin (G/C) backbone chemotherapy as standard of care (SoC) for the next-line treatment. Docetaxel Arm: Subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) cancer who have no therapeutic alternative with proven survival benefit or who are eligible for docetaxel (DTX) backbone chemotherapy as SoC for the next-line treatment. Phase 2: Subjects with locally advanced or metastatic colorectal cancer (mCRC), NSCLC, or biliary tract cancer (BTC) who are eligible for mFOLFOX, DTX, or G/C treatment, respectively.

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: November 11, 2021
• Study Start: September 22, 2021
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); FR (4)