A Study of AK104 in Subjects With Locally Advanced Unresectable or Metastatic MSI-H/dMMR Solid Tumors

A Single-arm, Open-label, Multicenter, Phase II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Locally Advanced Unresectable or Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors

It is a single-arm, open-label, multicenter, phase II study to evaluate the safety, efficacy, pharmacokinetics (PK) and immunogenicity of AK104 as a single agent in subjects with previously-treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors.

Study Overview

• Status: Terminated
• Conditions: MSI-H/dMMR Solid Tumor
• Intervention / Treatment: Drug: AK104

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have signed written informed consent form voluntarily.
• Male or female, age ≥ 18 years on the day of signing informed consent form.
• ECOG of 0 or 1.
• Estimated life expectancy of ≥3 months.
• Histologically or cytologically documented locally advanced unresectable or metastatic solid tumors.
• Confirmed MSI-H/dMMR status by the central laboratory.
• Have experienced documented disease progression during or after at least first-line therapy.
• Have radiologically measurable disease based on RECIST 1.1.
• Adequate organ function.
• Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.

Exclusion Criteria:

• Prior use of investigational products or devices within 4 weeks prior to C1D1 (Cycle 1 Day 1, the first dose of study drug).
• Presence of active autoimmune disease that have received systematic treatment in the past 2 years; or that is judged to be possibly relapsed or requires planned treatment by investigators.
• Active inflammatory bowel disease or that required treatment (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
• Prior use of systematic corticosteroid (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to C1D1.
• Prior exposure to tumor immunotherapy, such as checkpoint inhibitors (eg. anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody), checkpoint agonists or cellular therapy.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known presence or history of interstitial lung disease.
• History of gastrointestinal perforation and/or fistula within 6 months prior to C1D1.
• Serious infections within 4 weeks prior to C1D1.
• Known presence of active tuberculosis.
• Known untreated chronic hepatitis B or chronic hepatitis B virus DNA exceeding 1000 IU/ mL or active hepatitis C virus.
• Receipt of recent radiotherapy or anti-tumor treatment within 4 weeks prior to C1D1.
• Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease or central nervous system metastasis, with some exceptions.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria. Hair loss is excluded
• Known history of sever hypersensitivity reaction to other monoclonal antibodies.
• Known history of allergy or hypersensitivity to AK104 or any of its components.
• Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AK104	Drug: AK104; AK104，6 mg/kg IV，every 2 weeks (Q2W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with confirmed CR, PR, or SD, based on RECIST v1.1	Up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Overall survival (OS)	OS is defined as the time from the start of treatment with AK104 until death due to any cause.	Up to 2 years
Adverse events (AEs)	Incidences of treatment-emergent adverse events (TEAEs) , treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0	From first dose of AK104 through to 90 days after last dose of AK104
Observed pharmacokinetics (PK) exposure of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of AK104 through to 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable ADAs.	From first dose of AK104 through to 90 days after last dose of AK104

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Akeso Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2020
• Primary Completion (ACTUAL): September 30, 2022
• Study Completion (ACTUAL): September 30, 2022

Study Registration Dates

• First Submitted: September 7, 2020
• First Submitted That Met QC Criteria: September 7, 2020
• First Posted (ACTUAL): September 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AK104-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No