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Phase 2 Study of DKN-01 in Colorectal Cancer (DeFianCe)

L

Leap Therapeutics

Status and phase

Active, not recruiting
Phase 2

Conditions

Colorectal Adenocarcinoma
Colo-rectal Cancer
Colorectal Cancer Metastatic
Colorectal Cancer

Treatments

Drug: Bevacizumab
Drug: FOLFOX
Drug: FOLFIRI
Drug: DKN-01

Study type

Interventional

Funder types

Industry

Identifiers

NCT05480306
DEK-DKK1-P207

Details and patient eligibility

About

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

Full description

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

In Parts A and B, approximately 200 evaluable adult advanced CRC patients with measurable disease (RECIST v1.1) who have radiographically progressed during or following 1 line of systemic treatment will be enrolled in the study.

The study consists of a Screening Period, a Treatment Period, a Safety Follow-up Period (SFUP) and a Long-Term Follow-up Period (LTFU). Patients will be followed in the SFUP for approximately 30 days (+7 days) after the last administration of study drug and then enter the LTFU period to be followed for survival and subsequent therapies. Additionally, patients that ended study treatment for a reason unrelated to progressive disease [PD] will also be followed for disease progression in the LTFU period.

Enrollment

189 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Adult patients with advanced CRC with measurable disease (RECIST v1.1) who have radiographically progressed during or following one line of systemic treatment will be enrolled in the study.

Inclusion Criteria:

Patients meeting all of the following criteria will be considered eligible for study entry:

  1. Disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion criteria).

    • Patients may have received prior neoadjuvant or adjuvant therapy which could have included irinotecan or oxaliplatin. If progression has occurred within 12 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the one line of systemic therapy for advanced disease.

    • If assigned to receive FOLFIRI, patient may have received no prior irinotecan as part of first-line systemic therapy.
    • If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as part of first line systemic therapy.
    • Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line and/or maintenance systemic therapy.
  2. Able to provide written informed consent for any study specific procedures.

  3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1

  4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred], or archived tissue block specimen).

  5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function

  6. Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for study entry:

  1. Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer.
  2. Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other antibody or drug specifically targeting T-cell co-stimulation or coinhibitory checkpoint.
  3. Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
  4. Major surgery within 28 days prior to first dose of study drug.
  5. Prior radiation therapy within 14 days prior to first dose of study drug.
  6. Active leptomeningeal disease or uncontrolled brain metastases.
  7. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
  8. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  9. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
  10. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
  11. Serious nonmalignant disease
  12. Pregnant or nursing.
  13. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
  14. Known osteoblastic bony metastasis.
  15. Major surgery 28 days prior to study entry.
  16. Prior radiation therapy within 14 days prior to study entry.
  17. Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient.
  18. Active substance abuse.
  19. Known dihydropyrimidine dehydrogenase deficiency.
  20. Administration of a live vaccine within 28 days before first dose of study drug

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

189 participants in 2 patient groups

Treatment
Experimental group
Description:
DKN-01 + FOLFIRI or FOLFOX + bevacizumab
Treatment:
Drug: DKN-01
Drug: FOLFIRI
Drug: FOLFOX
Drug: Bevacizumab
Control
Active Comparator group
Description:
FOLFIRI or FOLFOX + bevacizumab
Treatment:
Drug: FOLFIRI
Drug: FOLFOX
Drug: Bevacizumab

Trial contacts and locations

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Central trial contact

Cynthia Sirard, MD; Elizabeth Parker

Data sourced from clinicaltrials.gov

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