A Study of RC48-ADC Combination Therapies as First-line Treatment in Advanced Metastatic Gastric Cancer

RemeGen

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Gastric Cancer

Treatments: Drug: Oxaliplatin（130mg/m2 ）; Drug: RC48-ADC（2.0mg/kg）; Drug: Trastuzumab; Drug: Toripalimab; Drug: Capecitabine（1000mg/m2）; Drug: Capecitabine（750mg/m2）; Drug: RC48-ADC（2.5mg/kg）; Drug: Oxaliplatin（100mg/m2 ）

Study type: Interventional

Funder types: Industry

Identifiers

NCT05980481

RC48-C027

Details and patient eligibility

About

This is a Phase II/III, randomized, multicenter, open-label clinical trial designed to evaluate safety and efficacy of RC48-ADC combine with Toripalimab and chemotherapy or RC48-ADC combine with Toripalimab and Trastuzumab as first-line treatment in human epidermal growth factor receptor 2 (HER2)-expression or non-expression participants with locally advanced or metastatic gastric cancer.

Enrollment: 201 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Voluntary agreement to provide written informed consent.
• Age:18-75 years（including 18 and 75）.
• Predicted survival ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function.
• All subjects must have inoperable, advanced or metastatic gastric or or gastroesophageal adenocarcinoma.
• Subject must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted;
• HER2-expressing status determined by laboratory to be IHC 1+, 2+ or 3+ or IHC0.

Exclusion criteria

• Active central nervous system (CNS) metastases.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, thyroid cancer ,etal.
• Known hypersensitivity to antibody-drug conjugate(ADC) or PD-(L)1 or any of its components.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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201 participants in 8 patient groups

RC48-ADC+Toripalimab+CAPOX (HER2-high expression)

Experimental group

Description:

Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: RC48-ADC（2.5mg/kg）

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: Oxaliplatin（130mg/m2 ）

RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression)

Experimental group

Description:

Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and Trastuzumab every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: RC48-ADC（2.5mg/kg）

Drug: Toripalimab

Drug: Trastuzumab

RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)

Experimental group

Description:

Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Oxaliplatin（100mg/m2 ）

Drug: RC48-ADC（2.5mg/kg）

Drug: Capecitabine（750mg/m2）

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: RC48-ADC（2.0mg/kg）

Drug: Oxaliplatin（130mg/m2 ）

Toripalimab+Trastuzumab+CAPOX (HER2-high expression)

Active Comparator group

Description:

Participants with HER2-high expression (IHC2+FISH+ or IHC3+) will receive of Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: Trastuzumab

Drug: Oxaliplatin（130mg/m2 ）

Toripalimab+CAPOX (HER2- intermediate/low expression)

Active Comparator group

Description:

Participants with HER2- intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: Oxaliplatin（130mg/m2 ）

RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression)

Experimental group

Description:

Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and Capecitabine every 3 weeks (Q3W), as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: RC48-ADC（2.5mg/kg）

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: Trastuzumab

RC48-ADC+Toripalimab+CAPOX (HER2-negative)

Experimental group

Description:

Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Oxaliplatin（100mg/m2 ）

Drug: RC48-ADC（2.5mg/kg）

Drug: Capecitabine（750mg/m2）

Drug: Toripalimab

Drug: RC48-ADC（2.0mg/kg）

Toripalimab+CAPOX (HER2- negative)

Active Comparator group

Description:

Participants with HER2- negative (IHC 0) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Treatment:

Drug: Capecitabine（1000mg/m2）

Drug: Toripalimab

Drug: Oxaliplatin（130mg/m2 ）