Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)

Clinical Trial Details

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 colorectal cancer patients.

In Parts A and B, approximately 150 evaluable adult advanced colorectal cancer patients with measurable disease who have radiographically progressed during or following 1 line of systemic treatment will be enrolled in the study.

DKN-01 plus FOLFIRI/FOLFOX and bevacizumab is considered investigational, which means that this combination has not yet been approved by the U.S. Food and Drug Administration (FDA). FOLFIRI/FOLFOX and bevacizumab are FDA-approved.

Participants will be randomized to receive either DKN-01 plus FOLFIRI/FOLFOX and bevacizumab or standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab]. Randomization is like flipping a coin and there is a 50/50 chance of being assigned to either group.

All treatments are given via intravenous (IV) infusion. The study team will discuss infusion specifics with each participant.

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 the 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.

The length of time participants will be in this study and the number of study visits depends on the response to the study drug regimen.

Key Eligibility:

Inclusion Criteria:

Colorectal cancer disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease
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.

Exclusion Criteria:

Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer.
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.
Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
Major surgery within 28 days prior to first dose of study drug.
Prior radiation therapy within 14 days prior to first dose of study drug.

Detailed eligibility will be discussed when reaching out to the study team.

Return to List

Study contact by location

Upper East Side - Manhattan

Contact(s)

Melissa Mow
646-962-3378
mem9233@med.cornell.edu

Primary Investigator(s)

Despina Siolas, MD, PhD

Protocol ID(s)

Weill Cornell Medicine IRB #:

2211025410

ClinicalTrials.gov:

NCT05480306

Status

Open to Enrollment

Age Group

Adult

Disease

Colon and Colorectal Cancer