An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

JRCT ID: jRCT2031230074

Registered date:15/05/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
• Date of first enrollment: 23/07/2023
• Target sample size: 360
• Countries of recruitment: China,Japan,Sourth Korea,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States of America,Japan
• Study type: Interventional

Intervention(s)

- Substudy 1:
Volrustomig 750 mg IV (Q3W) plus XELOX (Q3W) or Volrustomig 750 mg IV (Q3W) plus FOLFOX (Q2W)

- Substudy 2:
Rilvegostomig 750 mg IV (Q3W) plus XELOX (Q3W) or Rilvegostomig 750 mg IV (Q3W) plus FOLFOX (Q2W)

- Substudy3
AZD0901 2.2 mg/kg IV (Q3W) plus volrustomig 500 mg IV (Q3W) and 5-fluorouracil (Q3W) or AZD0901 2.2 mg/kg IV (Q3W) plus volrustomig 500 mg IV (Q3W) and capecitabine (Q3W)

- Substudy4
AZD0901 2.2 mg/kg IV (Q3W) plus rilvegostomig 750 mg IV (Q3W) and 5-fluorouracil (Q3W) or AZD0901 2.2 mg/kg IV (Q3W) plus rilvegostomig 750 mg IV (Q3W) and capecitabine (Q3W)

- Substudy5
AZD7789 1500mg IV (Q3W) plus XELOX (Q3W) or AZD7789 1500 mg (Q3W) plus FOLFOX (Q2W)

- Substudy6
AZD0901 2.2 mg/kg IV (Q3W) plus AZD7789 1500 mg IV (Q3W) and 5-fluorouracil (Q3W) or AZD0901 2.2 mg/kg IV (Q3W) plus AZD7789 1500 mg IV (Q3W) and capecitabine (Q3W)

Outcome(s)

Primary Outcome

ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by the Investigator at local site per RECIST 1.1.

PFS is defined as the time from the start of study intervention until progression per RECIST 1.1 as assessed by the Investigator at the local site or death due to any cause in the absence of progression.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Body weight > 35 kg.

- Previously untreated for unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (excluding undifferentiated carcinoma per the histological classification of gastric tumours in the fifth edition of the WHO classification of 2019).

- Prior neo-adjuvant and/or adjuvant chemotherapy, radiotherapy and/or chemoradiotherapy for gastric cancer or GEJ cancer are acceptable, but the last administration of the prior regimen (whichever was given last) must have been completed at least 6 months prior to the diagnosis of unresectable or metastatic disease. Diagnosis of unresectable or metastatic disease must be within the 3 months before treatment allocation. Palliative radiotherapy is allowed and must be completed 2 weeks prior to treatment allocation.

- Willing and able to provide an adequate tumour sample (fresh or archived) for biomarker analyses.

- Has measurable target disease assessed by the Investigator based on RECIST 1.1. Tumour lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

- Has an EOCG performance status of 0 to 1.

- Must have a life expectancy of at least 12 weeks.

- Has adequate organ and bone marrow function within 14 days before treatment allocation

Exclude criteria

- Participants with HER2-positive (3+ by IHC, or 2+ by IHC and positive by ISH] or indeterminate gastric or GEJ carcinoma.

- Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression. Note: Participants previously treated for CNS metastases who are asymptomatic, clinically stable, and who do not require corticosteroids (at doses > 10 mg of prednisone or equivalent) for at least 14 days prior to the first dose of study intervention are not excluded.

- Participants with ascites which cannot be controlled with appropriate interventions.

- Active infectious disease(s):
(a) Active infection including TB (clinical evaluation that includes clinical history, physical examination, and radiographic findings and TB testing in line with local practice).
(b) Human immunodeficiency virus infection. Participants should be tested for HIV prior to treatment allocation if required by local regulations or IRB/IEC.
(c) Chronic or active or uncontrolled hepatitis B. Refer to Section 8.2.4.
(d) Chronic or active or uncontrolled hepatitis C, defined as anti-HCV IgM/IgG positive and HCV-RNA detectable by PCR.
(e) Active hepatitis A: HAV-IgM positive.

- Uncontrolled intercurrent illness.

- Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment.

- Known DPD enzyme deficiency based on local laboratory testing where testing is SoC.

- Known allergy or hypersensitivity to BSP agents or any of the excipients of the BSP agents.

- Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment.

- Any prohibited medication listed in Protocol. Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention should be excluded, The following are exceptions to this criterion:

(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection).
(b) Systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone or equivalent.
(c) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
(d) A single dose for palliative purpose (eg, pain control).

- Major surgery within 4 weeks prior to the first dose of study intervention or still recovering from prior surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable.

- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study intervention.

Related Information

• Primary Sponsor: Yoshimoto Yusuke
• Secondary ID(s): NCT05702229