A Parallel Arm Phase 1b/2a Study of DKN-01 as Monotherapy or in Combination With Docetaxel for the Treatment of Advanced Prostate Cancer With Elevated DKK1

NCT03837353 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-01747
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

This is a non-randomized multi-center Phase 1b/2a dose escalation and dose expansion study testing DKN-01 as monotherapy or in combination with docetaxel in metastatic castration-resistant prostate cancer. Patients need to be biomarker positive (Dickkopf-1 \[DKK1\]) either in plasma or biopsy. Other biopsies for correlative studies are encouraged but not mandatory. Pharmacokinetic (PK) testing of one pre-treatment blood sample and one post-treatment blood sample will be mandatory on Day 1 of every cycle.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Dose Limiting Toxicities Observed by End of Treatment Cycle 1

  Measured among Phase I dose-escalation cohorts (arms 1A.1, 1A.2, 2A.1, and 2A.2) only.

  Up to End of Cycle 1 (Up to Day 21 for Cohort 1A, Up to Day 28 for Cohort 2A)

• Number of Participants With a Best Overall Response of Complete Response (iCR) or Partial Response (iPR) Per iRECIST by End of Long-Term Follow-Up Period

  iRECIST will be used by the Investigator to assess tumor response and progression. An iCR is defined as the disappearance of all target lesions as assessed by iRECIST; an iPR is defined as 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 iRECIST.

  Up to Year 2 Post-Baseline

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Up to Year 2 Post-Baseline

• Number of Participants With a Decline in Prostate-Specific Antigen (PSA) of at Least 50% Relative to Baseline

  Up to Year 2 Post-Baseline

• Maximal Percent Change in PSA Measured After Treatment Initiation

  Up to Year 2 Post-Baseline

Study Arms (4)

Cohort 1A

EXPERIMENTAL

In dose-escalation Cohort 1A, the dose of docetaxel 75 mg/m2 will remain fixed. The DKN-01 dose level will start with 300 mg and be escalated to 600 mg or de-escalated to 150 mg depending on the absence or presence of identified DLTs. DKN-01 will be administered in combination with docetaxel on Day 1 and as monotherapy on Day 15 of each 21-day cycle. Patients will be treated with the combination of DKN-01 and Docetaxel until Prostate Cancer Working Group 3 (PCWG3) progression or unacceptable toxicity.

Drug: DKN-01; Drug: Docetaxel

Cohort 1B

EXPERIMENTAL

In dose-expansion Cohort 1B, either the maximum tolerated dose (MTD) or highest dose tested of DKN-01 in combination with docetaxel in Cohort 1A will be the dose used. The dose of docetaxel 75 mg/m2 will remain fixed. DKN-01 will be administered in combination with docetaxel on Day 1 and as monotherapy on Day 15 of each 21-day cycle. Patients will be treated with the combination of DKN-01 and Docetaxel until PCWG3 progression or unacceptable toxicity.

Drug: DKN-01; Drug: Docetaxel

Cohort 2A

EXPERIMENTAL

In dose-escalation Cohort 2A, DKN-01 dose level will start with 300 mg and be escalated to 600 mg or de-escalated to 150 mg depending on the absence or presence of identified DLTs. DKN-01 will be administered as monotherapy on Days 1 and 15 of each 28-day cycle. Patients will be treated with DKN-01 until PCWG3 progression or unacceptable toxicity.

Drug: DKN-01

Cohort 2B

EXPERIMENTAL

In dose-expansion Cohort 2B, the MTD or highest dose tested of DKN-01 monotherapy in Cohort 2A will be the dose used. DKN-01 will be administered as monotherapy on Days 1 and 15 of each 28-day cycle. Patients will be treated with DKN-01 until PCWG3 progression or unacceptable toxicity.

Drug: DKN-01

Interventions

DKN-01 DRUG

DKN-01 is a large molecular weight protein that will be given as a flat dose on a Days 1 and 15 of a 21-day cycle in Dose-Escalation Cohort 1A and Dose-Expansion Cohort 1B. DKN-01 will be given on Days 1 and 15 on a 28-day cycle in Dose-Escalation Cohort 2A and Dose-Expansion Cohort 2B. The dose of DKN-01 will be administered as an intravenous (IV) infusion over 60 (±) 15 minutes.

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B

Docetaxel DRUG

Docetaxel will be administered as an IV infusion over approximately 60 (±15) minutes on day 1 of a 21-day cycle in Cohorts 1A and 1B. In Cohort 1A, docetaxel must be dosed at 75 mg/m2 on cycle 1 day 1. Docetaxel can be dosed at 75 mg/m2 or 60 mg/m2 in subsequent cycles depending on clinical discretion and dose modification guidelines. Regardless of dose, docetaxel must be dosed in 21-day cycles. In Cohort 1B, cycle 1 day 1 dosing of docetaxel will either be 75 mg/m2 or 60 mg/m2 depending on clinical discretion.

Cohort 1A; Cohort 1B

Eligibility Criteria

• Age: 18 Years - 100 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years.
• Have a histologically or cytologically confirmed cancer of prostate origin (adenocarcinoma, poorly differentiated carcinoma, or neuroendocrine carcinoma are all allowed).
• Patients with pure neuroendocrine carcinoma must have had at least one line of platinum-based chemotherapy unless the patient is intolerant of or is refusing chemotherapy.
• Patients with pure neuroendocrine carcinoma do not need to have been previously treated with androgen receptor (AR) signaling inhibitors (abiraterone or enzalutamide or apalutamide or darolutamide) but must have castrate testosterone and have castration-resistant disease.
• Surgically or medically castrated, with testosterone levels of \< 50 ng/dL (\< 2.0 nM). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to C1D1 and must be continued throughout the study.
• Cohort 1B. Patients must have measurable disease per RECIST v1.1 guidelines AND must have either:
• PSA progression is defined by Prostate Cancer Working Group 3 (PCWG3) criteria as a minimum of two consecutive rising levels, with an interval of ≥1 week between each determination with a minimum PSA of 1 ng/mL, if PSA is the sole evidence of progression, OR
• Radionuclide bone progression as defined by at least two new metastatic lesions (per PCWG3), OR
• Soft tissue progression on transaxial imaging: new or progressive soft tissue masses on computed tomography (CT) or magnetic resonance imaging (MRI) scans as defined by RECIST v1.1.
• Cohorts 1A, 2A, 2B. Patients must have baseline progression defined as one of the following:
• PSA progression is defined by PCWG3 criteria as a minimum of two consecutive rising levels, with an interval of ≥1 week between each determination with a minimum PSA of 2 ng/mL.
• Radionuclide bone progression as defined by at least two new metastatic lesions (per PCWG3).
• Soft tissue progression on transaxial imaging: new or progressive soft tissue masses on computed tomography (CT) or magnetic resonance imaging (MRI) scans as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Estimated life expectancy of at least 3 months, in the judgment of the Investigator.

You may not qualify if:

• Any anti-cancer therapy (with the exception of luteinizing hormone-releasing hormone \[LHRH\] analog or antagonist) within 2 weeks prior to initiation of study treatment.
• Any investigational anti-cancer therapy within 4 weeks of initiation of study treatment.
• New York Heart Association Class III or IV heart failure, or myocardial infarction within the past 6 months, or unstable arrhythmia within 3 months.
• Uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry.
• History of malignancy other than prostate cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as non-melanoma skin carcinoma or ductal carcinoma in situ.
• Known to be human immunodeficiency virus (HIV) positive, have positive hepatitis B surface antigen (HBSAg), or positive hepatitis C antibody (HCAb) test. (Hepatitis C antibody-positive patients with an undetectable hepatitis C virus (HCV) RNA will be eligible.)
• History of solid organ transplant (ie, heart, lungs, liver, or kidney).
• History of autologous/allogenic bone marrow transplant.
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator and/or Sponsor.
• Active or untreated central nervous system (CNS) malignancy or metastasis. Screening for CNS metastases of asymptomatic patients without a history of CNS metastases is not required. Patients with treated CNS metastases are eligible provided they meet all of the following criteria:
• Evaluable disease outside the CNS.
• No history of intracranial or intraspinal hemorrhage.
• No evidence of significant vasogenic edema.
• No ongoing requirement for corticosteroids as therapy for CNS disease. (Anti-convulsants at a stable dose for \> one month is allowed.)
• No stereotactic radiation, whole brain radiation within 4 weeks of C1D1.

Sponsors & Collaborators

• NYU Langone Health: lead
• Leap Therapeutics, Inc.: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Veterans Affairs New York Harbor Healthcare System

New York, New York, 10010, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Related Publications (1)

• Wise DR, Schneider JA, Armenia J, Febles VA, McLaughlin B, Brennan R, Thoren KL, Abida W, Sfanos KS, De Marzo AM, Yegnasubramanian S, Fox JJ, Haas M, Heath H, Kagey MH, Newman W, Sirard CA, Fleisher M, Morris MJ, Chen Y, Larson SM, Haffner MC, Nelson PS, Schultz N, Garabedian MJ, Scher HI, Logan SK, Sawyers CL; International SU2C/PCF Prostate Cancer Dream Team. Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer. JCO Precis Oncol. 2020 Sep 29;4:PO.20.00097. doi: 10.1200/PO.20.00097. eCollection 2020.

  PMID: 33015525 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: David Wise, MD, PhD
• Organization: NYU Langone Health

David.Wise@nyulangone.org

(212) 731-5405

Study Officials

• David Wise, MD, PhD

  New York Langone Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: February 12, 2019
• Study Start: April 1, 2019
• Primary Completion: July 19, 2022
• Study Completion: September 20, 2022
• Last Updated: December 18, 2023
• Results First Posted: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data.

Locations

US (5)