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Gastric AdenocarcinomaPhase 1/2NCT03852251

A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, for Advanced Solid Tumors or With mXELOX/XELOX as First-line Therapy for Advanced Gastric or GEJ Adenocarcinoma

A Phase 1/2 study testing AK104, Oxaliplatin and Capecitabine in people with Gastric Adenocarcinoma and Advanced Solid Tumors, run by Akeso at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activities of AK104，a PD-1/CTLA-4 bispecific antibody, when administered as a single agent in adults subjects with advanced or metastatic solid tumors, or combined with… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
AK104, Oxaliplatin and Capecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
338 participants
Where
1 siteChina
Study dates
18 Jan 2019to 25 Mar 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written and signed informed consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
  • Estimated life expectancy of ≥3 months.
  • For Phase Ib Cohort 1, histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available. For other cohorts in Phase Ib and Phase II, histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
  • For cohorts other than cohort 1 in Phase Ib and Phase II: No prior systemic chemotherapy for advanced or metastatic gastric or GEJ adenocarcinoma. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred >6 months from last treatment.
  • Subjects must have at least one measurable lesion in accordance with RECIST v1.1. A lesion previously treated with local therapies such as radiotherapy can be considered a target lesion if there is objective evidence of progression in the lesion.
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  • For cohorts other than cohort 1 in Phase Ib and Phase II: Subjects must provide an available tumor tissue samples taken < 6 months prior to first dose of study treatment.
  • Adequate organ function.
  • Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception.
  • Nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective method of contraception from Day 1 and for 120 days after the last dose of investigational product.

Who cannot join

  • Subjects with known HER2-positive gastric or GEJ adenocarcinoma (not applicable for Cohort 1 in Phase Ib).
  • Subjects squamous cell, undifferentiated or other histological types of with gastric or GEJ cancer (not applicable for Cohort 1 in Phase Ib).
  • Other invasive malignancies within 2 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
  • Receipt of last radiotherapy or any anti-tumor treatment [chemotherapy, targeted therapy, immunotherapy, Chinese patent drugs with antitumor indications, or immunomodulators or tumor embolization] within 4 weeks prior to the first dose of study treatment.
  • Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
  • Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
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  • Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea). Inability to swallow, malabsorption syndrome, uncontrollable nausea, vomiting, diarrhea, or other gastrointestinal diseases which significantly affect the absorption of administered drug.
  • Known history of primary immunodeficiency virus infection.
  • Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • Known history of interstitial lung disease.
  • Known history of active tuberculosis (TB).
  • Serious infections within 4 weeks prior to the first dose of study drug, including but not limited to complications requiring hospitalization, sepsis or severe pneumonia.
  • An active infection requiring systemic therapy.
  • Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
  • Known history of testing positive for human immunodeficiency virus (HIV).
  • Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
  • Clinically active hemoptysis, active diverticulitis, peritoneal abscess, or gastrointestinal obstruction.
  • Clinically significant bleeding symptoms or significant bleeding tendency such as gastrointestinal bleeding, hemorrhagic gastric ulcer or vasculitis within 1 month prior to the first dose of study treatment.
  • 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.
  • Receipt of live or attenuated vaccination within 30 days prior to the first dose of study treatment, or plan to receive live or attenuated vaccine during the study.
  • Known history of serious hypersensitivity reaction to other monoclonal antibodies.
  • Subjects with known contraindications to XELOX（refer to the package inserts of oxaliplatin and capecitabine）(not applicable for Cohort 1 in Phase Ib).
  • Known history of allergy or hypersensitivity to AK104 or any of its components (applicable for all cohorts in Phase Ib and Phase II), or oxaliplatin, other platinum compounds, capecitabine, or any of their components (not applicable for Cohort 1 in Phase Ib).
  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

Other trials in China

About this study

Official title: A Multicenter, Open-label, Phase Ib/II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Advanced Solid Tumors or AK104 in Combination With Oxaliplatin and Capecitabine As First-line Therapy in Subjects With Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activities of AK104，a PD-1/CTLA-4 bispecific antibody, when administered as a single agent in adults subjects with advanced or metastatic solid tumors, or combined with oxaliplatin and capecitabine as first-line therapy in adult subjects with advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Read the detailed description

The study consists of a dose escalation and expansion phase (Phase Ib) to determine the recommended Phase 2 dose (RP2D) for AK104 in combination with oxaliplatin and capecitabine, and a dose confirmation phase (Phase II) which will further characterize the treatment of AK104 in combination at the RP2D.

Being tested
AK104, Oxaliplatin, Capecitabine
Keywords
immuno-oncology, PD-1/CTLA-4 Bispecific, gastric or GEJ adenocarcinoma, PD-1, CTLA-4
Medical subject headings
Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AK104Biological

    Subjects will receive AK104 by intravenous administration.

  • OxaliplatinDrug

    Subjects will receive AK104 in combination with oxaliplatin and capecitabine.

  • CapecitabineDrug

    Subjects will receive AK104 in combination with oxaliplatin and capecitabine.

Study groups in NCT03852251
Study groupRoleWhat they receive
AK104ExperimentalAK104 IV every 2 weeks (q2w)
Receives: Biological: AK104
AK104 and chemotherapyExperimentalAK104 IV Q2W or Q3W，oxaliplatin IV 85 mg/m2 Q2W or 130mg/m2 Q3W，capecitabine 1000 mg/m2#twice a day (bid) for day 1to day 10 or day 1 to day 14 per cycle
Receives: Biological: AK104; Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of subjects experiencing adverse events (AEs) (Phase Ib)

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.

    Measured: From the time of informed consent through 90 days following termination of treatment with investigational product

  2. The number of subjects experiencing dose-limiting toxicities (DLTs) (Phase Ib)

    DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment.

    Measured: During the first 4 weeks

  3. Anti-tumor activity of AK104 using objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator (Phase II)

    The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.

    Measured: From the first dose of study drug through the date of first documented progression, end of study, date of death, or one year after the last patient starts treatment, whichever should occur first

Secondary outcomes (8)

  1. Disease control rate (DCR)

    The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.

    Measured: Up to 2 years

  2. Duration of response (DoR)

    Duration of response 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.

    Measured: Up to 2 years

  3. Progression-free survival (PFS)

    Progression-free survival 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.

    Measured: Up to 2 years

  4. Overall survival (OS)

    Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.

    Measured: Up to 2 years

  5. Maximum observed concentration (Cmax) of AK104

    The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.

    Measured: From first dose of AK104 through to 90 days after last dose of AK104

  6. Minimum observed concentration (Cmin) of AK104 at steady state

    The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.

    Measured: From first dose of AK104 through to 90 days after last dose of AK104

  7. Area under the curve (AUC) of AK104

    The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.

    Measured: From first dose of AK104 through to 90 days after last dose of AK104

  8. 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 anti-drug antibodies (ADAs).

    Measured: From first dose of AK104 through 90 days after last dose of AK104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2019
  2. Study start18 Jan 2019
  3. Primary completion25 Mar 2024
  4. Study completion25 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
338 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03852251
Sponsor's protocol ID
AK104-201
Status last verified
Jul 2024
First submitted
21 Feb 2019
Last updated
2 Aug 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Peng J, Zhu Q, Peng Z, Chen Z, Liu Y, Liu B. Patients with positive HER-2 amplification advanced gastroesophageal junction cancer achieved complete response with combined chemotherapy of AK104/cadonilimab (PD-1/CTLA-4 bispecific): A case report. Front Immunol. 2022 Dec 8;13:1049518. doi: 10.3389/fimmu.2022.1049518. eCollection 2022.

    PubMed 36569905

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AK104, Oxaliplatin and Capecitabine in people with Gastric Adenocarcinoma and Advanced Solid Tumors, run by Akeso at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of subjects experiencing adverse events (AEs) (Phase Ib) (time frame: From the time of informed consent through 90 days following termination of treatment with investigational product). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03852251, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.

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