Clinical trial NCT04982276: A Study of AK109 and AK104 in Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Official title: A Multicentre, Phase Ib/II Clinical Study of AK109 and AK104 With or Without Chemotherapy in Second-line Treatment of Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-07-29
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicentre, Phase Ib/II Clinical Study of AK109 and AK104 With or Without Chemotherapy in Second-line Treatment of Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma .


Eligibility criteria: Inclusion Criteria:

1. Written and signed informed consent
2. Age ≥ 18 years but ≤ 75 years
3. ECOG of 0 or 1.
4. Estimated life expectancy of ≥3 months.
5. Histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
6. At least one measurable lesion per RECIST v1.1.
7. Gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma with failure of first-line treatment with anti-PD-1/L1 and chemotherapy
8. Adequate organ function.
9. Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.

Exclusion Criteria:

1. Other invasive malignancies within 3 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.
2. Any previous systemic therapy targeting VEGF or anti-VEGFR signaling pathways.
3. In addition to PD1 or PD-L1,Prior exposure to 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).
4. Known history of primary immunodeficiency virus infection.
5. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
6. Known history of interstitial lung disease.
7. Known history of active tuberculosis (TB).
8. Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
9. Patients with untreated chronic hepatitis B or HBV DNA exceeding 500IU/mL or active hepatitis C should be excluded. Patients with HCV antibody positive are eligible to participate in the study if the results of HCV RNA test show negative.
10. Known history of testing positive for human immunodeficiency virus (HIV).
11. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
12. 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.
13. Pregnant or lactating women.

Primary outcomes:
measure: Number of subjects experiencing dose-limiting toxicities (DLTs)
timeFrame: During the first 4 weeks
measure: Adverse events (AEs)
timeFrame: up to 2 years
measure: Objective response rate (ORR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
measure: Observed pharmacokinetics (PK) exposure of AK109 and AK104
timeFrame: From first dose of AK109 and AK104 through 90 days after last dose of AK109 and AK104
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of AK109 and AK104 through 90 days after last dose of AK109 and AK104
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, MD
role: PRINCIPAL_INVESTIGATOR
References: