A Study of AK109 and AK104 in Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

Akeso

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma

Treatments: Biological: AK104; Drug: paclitaxel; Biological: AK109

Study type: Interventional

Funder types: Industry

Identifiers

NCT04982276

AK109-201

Details and patient eligibility

About

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 .

Enrollment: 138 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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138 participants in 2 patient groups

AK109 combined with chemotherapy

Experimental group

Description:

AK109 combined with paclitaxel, iv, every 3 weeks

Treatment:

Biological: AK109

Drug: paclitaxel

Drug: paclitaxel

AK104 and AK109 combined with chemotherapy

Experimental group

Description:

AK104 combined with AK109 and paclitaxel, iv, every 3 weeks

Treatment:

Biological: AK109

Drug: paclitaxel

Drug: paclitaxel

Biological: AK104