WaKING: Wnt and checKpoint INhibition in Gastric Cancer

NCT04166721 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CCR4976
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentre open-label non-randomised, Single Stage Ahern Design (with a 3+3 design for the safety run-in) phase II clinical trial of DKN-01 plus atezolizumab in patients with advanced unresectable or metastatic OGA who have progressed following chemotherapy.

Conditions

Metastatic Esophageal Cancer; Metastatic Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Safety run-in phase: To recommend a safe and tolerable dose of combination DKN-01 and atezolizumab for use in the main (Phase IIB efficacy) phase of this trial.

  Progression through dose levels will be determined by the occurence of dose limiting toxicities in the study population

  The DLT period is 28 days from the start of the combination of DKN-01 and atezolizumab for any given patient (i.e. from C2 D1)

• Main phase IIB (efficacy) phase: Best objective response rate (ORR) using RECIST 1.1 criteria

  ORR will be defined in the mITT population as the proportion of patients who have achieved CR or PR (as assessed according to RECIST 1.1 criteria) as their best overall response during treatment. The rate will be presented as a proportion with an exact 95% confidence interval.

  24 months

Secondary Outcomes (3)

• The safety of DKN-01 plus atezolizumab will be assessed in the Safety Population (SFP) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  Up to 135 days after the last dose

• Progression free survival (PFS) according to RECIST 1.1

  Up to 24 months

• Overall survival

  Up to 24 months

Study Arms (1)

DKN-01 and atezolizumab

EXPERIMENTAL

DKN-01 is an intravenous medication which will be given at a variable dose during the Phase IIA safety run in phase of the trial (150mg, 300mg or 600mg IV q14d). During the Phase IIB efficacy phase of the trial patients will be treated with DKN-01 at the safe and tolerated combination dose identified during the Phase IIA safety run in phase. Atezolizumab is a monoclonal antibody which is given via an intravenous infusion at a dose of 840mg on the first day of a two week cycle. (Day 1 q 14d) from cycle 2 onwards. In the first cycle of treatment, patients will be treated with only DKN-01, and following this they will be treated with both DKN-01 and atezolizumab

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Immunotherapy

Also known as: DKN-01

DKN-01 and atezolizumab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Male or female patients age ≥18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically or cytologically confirmed advanced or metastatic gastroesophageal adenocarcinoma. Patients with HER2 positive cancer are permitted after having received HER2 targeted therapy in first line as per Standard of Care
• Disease progression during or following treatment with one or two lines of treatment for advanced disease, one of which must have been a platinum and fluoropyrimidine combination.
• Measurable, or non-measurable but evaluable, disease per RECIST v1.1
• Evidence of tumor mismatch repair proficiency and/or MSI stability through testing of a representative tumor tissue specimen using immunohistochemistry for MMR proteins or MSI testing. Local testing or historical results of archival tumour tissue is satisfactory for trial entry.
• ECOG 0-1
• Life expectancy ≥ 3 months as per physician judgment
• Adequate hematologic and end-organ function, defined by the following laboratory test results:
• a. ANC ≥ 1.5 x 109/L without granulocyte colony-stimulating factor support b. Lymphocyte count ≥ 0.5 x 109/L c. Platelet count ≥ 100 x 109/L without transfusion d. Hemoglobin ≥ 90 g/L (9 g/dL) (patients may be transfused to meet this criterion) e. AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions: i. Patients with documented liver metastases: AST and ALT ≤ 5 x ULN ii. Patients with documented liver or bone metastases: ALP ≤ 5 x ULN f. Serum bilirubin ≤ 1.5 x ULN with the following exception: i. Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN g. Serum creatinine ≤ 1.5 x ULN or Creatinine clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)} h. Serum albumin ≥ 25 g/L (2.5 g/dL) i. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN j. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen k. Negative hepatitis B surface antigen (HBsAg) test at screening l. Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA \< 500 IU/mL at screening m. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
• n. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening o. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
• Tumour is amenable to safe repeated biopsies and patient agrees to undergo biopsies for translational endpoints.
• In patients who are receiving anticoagulation, stopping anticoagulation for biopsies must be deemed safe by the treating team.
• Patients on oral anticoagulation are required to change to low molecular weight heparin prior to study entry to be eligible.

You may not qualify if:

• Any contraindication or known hypersensitivity reaction to any of the study drugs
• Persisting toxicity relating to prior therapy of \>grade 1 CTCAE version 5.0 except alopecia of any grade and neuropathy ≤ grade 2, or other grade ≤2 not constituting a safety risk based on investigators judgement
• Any prior treatment with immunotherapy including anti-PD-1or PD-L1 therapy
• known active or untreated CNS metastases are excluded. Patients with treated and asymptomatic CNS metastases are eligible, if they meet all of the following:
• Evaluable or measurable disease outside the CNS
• No metastases to midbrain, pons, medulla, or within 10 mm of the optic nerves and chiasm
• No history or evidence of intracranial haemorrhage or spinal cord haemorrhage
• No evidence of clinically significant vasogenic oedema
• Not on corticosteroids for ≥ 2 weeks; anti-convulsants at a stable dose are allowed
• No evidence of clinical and radiographic disease progression in the CNS ≥ 3 weeks after radiotherapy or surgery
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 5.0), any history of anaphylaxis
• Any Immunodeficiency disorder
• Patients with another active malignancy or a prior malignancy within the past 5 years are excluded, except patients with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
• History of autoimmune disease except for the following:
• Patients with autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 18, 2019
• Study Start: February 11, 2020
• Primary Completion: March 30, 2025
• Study Completion: December 31, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

GB (1)