Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY2812176, Formerly LY2812176
DKN-01 · 6 trials · 20 indications
PFS, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC.
Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)
Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)
Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03).
SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone
Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B.
Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category.
For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
| Arm | Type | Description |
|---|---|---|
| Treatment | EXPERIMENTAL | DKN-01 + FOLFIRI or FOLFOX + bevacizumab |
| Control | ACTIVE_COMPARATOR | FOLFIRI or FOLFOX + bevacizumab |
| DKN-01 monotherapy in recurrent EEC | EXPERIMENTAL | 300mg DKN-01 monotherapy in recurrent EEC |
| DKN-01+paclitaxel in recurrent EEC | EXPERIMENTAL | 300mg DKN-01+paclitaxel in recurrent EEC |
| DKN-01 monotherapy in recurrent EOC | EXPERIMENTAL | 300mg DKN-01 monotherapy in recurrent EOC |
| DKN-01+paclitaxel in recurrent EOC | EXPERIMENTAL | 300mg DKN-01+paclitaxel in recurrent EOC |
| DKN-01 monotherapy in carcinosarcoma | EXPERIMENTAL | 600mg DKN-01 monotherapy in carcinosarcoma |
| DKN-01 +paclitaxel in carcinosarcoma | EXPERIMENTAL | 600mg DKN-01 +paclitaxel in carcinosarcoma |
| 150 mg DKN-01 Part A | EXPERIMENTAL | Patients will receive 150 mg of DKN-01 followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle. |
| 300 mg DKN-01 Part A | EXPERIMENTAL | Patients will receive 300 mg of DKN-01 followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle. |
| MTD mg DKN-01 Part B | EXPERIMENTAL | Patients are treated at the maximum tolerated dose (MTD) of DKN-01 (or highest dose tested in Part A if the MTD is not defined) followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle. |
| DKN-01 150 mg plus paclitaxel | EXPERIMENTAL | DKN-01 150 mg administered on Days 1 and 15 and paclitaxel 80 mg per meter squared of body surface area (mg/m2) administered on Days 1, 8, 15, and 22 |
| DKN-01 300 mg plus paclitaxel | EXPERIMENTAL | DKN-01 300 mg administered on Days 1 and 15 and paclitaxel 80 mg per meter squared of body surface area (mg/m2) administered on Days 1, 8, 15, and 22 |
| DKN-01 150 mg plus pembrolizumab | EXPERIMENTAL | DKN-01 150 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1 |
| DKN-01 300 mg plus pembrolizumab | EXPERIMENTAL | DKN-01 300 mg administered on Days 1 and 15 and pembrolizumab 200 mg administered on Day 1 |
| DKN-01 300 mg monotherapy | EXPERIMENTAL | DKN-01 300 mg administered on Days 1 and 15 |
| DKN-01 300mg | EXPERIMENTAL | DKN-01 plus lenalidomide (Revlimid)/dexamethasone |
| DKN-01 600mg | EXPERIMENTAL | DKN-01 plus lenalidomide (Revlimid)/dexamethasone |
| Standard of Care | ACTIVE_COMPARATOR | Lenalidomide (Revlimid)/dexamethasone |
| 75 milligram (mg) DKN-01 Part A | EXPERIMENTAL | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 600 mg DKN-01 Part A | EXPERIMENTAL | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 300 mg DKN-01 Part B | EXPERIMENTAL | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
| Name | Type | Description |
|---|---|---|
| DKN-01 | DRUG | 30 minute IV infusion (400mg) every two weeks with an additional loading dose in the first cycle of treatment |
| FOLFIRI | DRUG | 90-min IV infusion of irinotecan, leucovorin, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks |
| Bevacizumab | DRUG | 90-min IV infusion (5mg) |
| FOLFOX | DRUG | 2 hour IV infusion of oxaliplatin, folinic acid, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks |
| Paclitaxel | DRUG | Administered by IV infusion |
| 300mg DKN-01 | DRUG | Administered by IV infusion |
| 600mg DKN-01 | DRUG | Administered by IV infusion |
| gemcitabine | DRUG | Administered by IV infusion. |
| cisplatin | DRUG | Administered by IV infusion |
| DKN-01 150 mg | DRUG | Administered by IV infusion |
| Pembrolizumab | DRUG | Administered by IV infusion |
| DKN-01 300 mg | DRUG | Administered by IV infusion |
| DKN-01 600 mg | DRUG | 600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone |
| Standard of Care | DRUG | Current approved standard of care |
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 ent...
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DKN-01 is an investigational small molecule oncology drug developed by Cypherpunk Technologies Inc. (ticker CYPH). It is being studied in several cancer types, including cancers of the intrahepatic and extra-hepatic biliary system, colorectal cancer, endometrial cancer, esophageal neoplasms, and multiple myeloma. It is not approved and remains in clinical development.
DKN-01 targets DKK1, a protein in the Dickkopf family. DKN-01 is classified as an inhibitor of DKK1. By binding DKK1, the drug is designed to interfere with DKK1-mediated signaling in the tumor microenvironment. This mechanism is being evaluated in oncology indications including biliary tract cancer, colorectal cancer, and endometrial cancer.
DKN-01 is developed by Cypherpunk Technologies Inc., which trades under the ticker CYPH. The company has sponsored clinical studies of DKN-01 across multiple cancer types, including colorectal cancer, endometrial and ovarian cancer, biliary tract carcinoma, and esophageal and gastroesophageal cancers.
DKN-01 is in Phase 1 development according to its current development stage, and it is investigational rather than approved. Completed studies include Phase 1 and Phase 2 trials in biliary tract cancer, colorectal cancer, endometrial and ovarian cancer, and esophageal and gastroesophageal cancers. No active trials are currently listed for DKN-01.
Completed DKN-01 trials include NCT05480306, a Phase 2 study in colorectal cancer with 188 patients across the United States, Germany, and South Korea, and NCT03395080, a Phase 2 study in endometrial, ovarian, and uterine cancer with 111 patients. Phase 1 studies include NCT02375880 in biliary tract and gallbladder carcinoma and NCT02013154 in esophageal and gastroesophageal cancers.