A Study of RC118 Plus Toripalimab / RC148 in Patients with Locally Advanced Unresectable or Metastatic Solid Tumors

NCT ID: NCT06038396

Last Updated: 2025-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-03

Study Completion Date

2026-08-31

Brief Summary

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This is an open, multi-center, dose escalation and expansion phase I/II study. The Phase I study will explore the tolerability and safety of RC118 in combination with Toripalimab for the treatment of patients with Claudin 18.2-positive, locally advanced unresectable or metastatic malignant solid tumors, and to establish the maximum tolerated dose (MTD) and the recommended dose in phase II clinical trials (RP2D); The Phase II study will evaluate the efficacy and safety of RC118 in combination with Toripalimab or RC148 in patients with locally advanced or metastatic Gastric cancer/Gastro-esophageal junction cancer.

Detailed Description

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Conditions

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Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A-RC118 plus Toripalimab

Participants receive RC118- ADC(dose A or dose B) Q2W and Toripalimab (fixed dose) Q3W

Group Type EXPERIMENTAL

RC118

Intervention Type DRUG

Dose A or dose B, Q2W

Toripalimab

Intervention Type DRUG

Fixed dose, Q3W

Part B-RC118 plus Toripalimab / RC148

Referring to the results of the Part A, an extension cohort using RC118 plus Toripalimab /RC148 will be established.

Group Type EXPERIMENTAL

RC118

Intervention Type DRUG

Dose A or dose B, Q2W

Toripalimab

Intervention Type DRUG

Fixed dose, Q3W

RC148

Intervention Type DRUG

Fixed dose, Q3W Other Names: RC148 injection

Interventions

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RC118

Dose A or dose B, Q2W

Intervention Type DRUG

Toripalimab

Fixed dose, Q3W

Intervention Type DRUG

RC148

Fixed dose, Q3W Other Names: RC148 injection

Intervention Type DRUG

Other Intervention Names

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RC118 for injection Toripalimab injection JS001

Eligibility Criteria

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Inclusion Criteria

1. Be able to participate in the study voluntarily and willing to provide written informed consent.
2. male or female 18 ≤ age ≤ 75 years old.
3. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4. The expected survival ≥12 weeks.
5. Enrollment of subjects with locally advanced or metastatic gastric adenocarcinoma/adenocarcinoma of the gastroesophageal junction who have a histologically confirmed diagnosis and have failed standard therapy.
6. Subjects who received ≤2 prior systemic therapies.
7. Subjects agree to provide tumor tissue specimens for Claudin 18.2 and PD-L1 expression levels during the screening period. Samples should have moderate to high expression of Claudin 18.2 by membrane staining.
8. According to the RECIST v1.1, there is at least one measurable target lesion.
9. Sufficient heart, bone marrow, liver and kidney functions.
10. Fertile male or female subjects must agree to take effective contraceptive measures during the study period and for 6 months after the end of the last dose, such as double-barrier contraceptive methods(eg. condoms), oral or injectable contraceptives, intrauterine.

Exclusion Criteria

1. Pregnant women, breastfeeding women or women with a positive blood pregnancy test result during the screening period (non-fertile women do not need to undergo a pregnancy test, such as women with a previous hysterectomy and/or bilateral oophorectomy or amenorrhea ≥12 months).
2. Subjects with active hepatitis B (HBsAg positivity and HBV DNA titre higher than the normal upper limit), active hepatitis C (HCVAb positivity and HCV RNA titre higher than the normal upper limit), and positive human immunodeficiency virus antibody (HIV-Ab) results during the screening period.
3. Subjects with a history of other acquired or congenital immunodeficiency diseases, or who have undergone organ or bone marrow transplantation.
4. Subjects who have previously received monoclonal antibody, double antibody targeting drugs, ADC, CAR-T and other therapeutic drugs targeting Claudin 18.2 or other ADCs with MMAE payload; or have participated in clinical trials and received investigational drugs within 4 weeks before the first dose.
5. Have vaccinated within 4 weeks prior to the first dose or plan to receive any live vaccine during the study.
6. Subjects are atallergic to the ingredients or excipients of the experimental drug.
7. Subjects who have received anti-tumor therapy (chemotherapy, radiotherapy, immunotherapy, or targeted therapy) within 4 weeks or less than 5 half-lives of the experimental drug prior to the start of the first dose; or who have received anti-tumor therapy with traditional Chinese medicine or immunomodulators within 2 weeks prior to the start of the first dose.
8. The toxicity of previous anti-tumor therapy has not returned to the level 0 or 1 as defined by NCI-CTCAE v5.0 (except for alopecia, pigmentation and other long-term toxicity ≤2 that cannot be recovered which was defined by investigators).
9. The clinical symptoms of pleural effusion, abdominal effusion, or pericardial effusion that requires drainage.
10. Active infection within 2 weeks prior to the first dose that requires systemic anti-inflammatory therapy.
11. Complicating other diseases that seriously endanger the safety of the subjects or affect the completion of the study, such as peptic ulcer, intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, renal failure and uncontrolled diabetes (Fasting blood glucose \> 8.5 mmol/L, HbA1C ≥7.5%).
12. The tumor lesion has a bleeding tendency or has received blood transfusion treatment within 4 weeks prior to the first dose.
13. During the screening period, QTc interval \>450 ms(male), QTc interval \>470ms(female); previous family or personal history of long/short QT interval syndrome; A history of ventricular arrhythmia deemed clinically significant by the investigator, or currently receiving antiarrhythmic medication, or implantation of arrhythmia defibrillation device.
14. Previous myocardial infarction (within 6 months prior to the first dose), severe or unstable angina, coronary or peripheral artery bypass grafting, heart failure grade 3\~4 defined by New York Heart Association (NYHA) and uncontrolled hypertension.
15. Experienced an arterial/venous thromboembolic event within 6 months prior to the study.
16. Active autoimmune disease that requires systemic treatment within 2 years prior to the study. Patients with vitiligo, psoriasis, alopecia or Grave's disease that not requires systemic treatment, hypothyroidism that only requires thyroid hormone replacement therapy, and type 1 diabetes only requires insulin replacement therapy may be included in the study.
17. Subjects with brain metastases and/or carcinomatous meningitis who have previously received related treatment may be considered for inclusion if their disease has been stable for at least 3 months, no imaging evidence of disease progression has been observed within 4 weeks prior to the first dose, all neurological symptoms have returned to baseline, and radiation, surgery, or steroid therapy has been discontinued at least 28 days prior to the first dose; cancerous meningitis should be excluded regardless of whether it is clinically stable.
18. Other malignant tumor within 5 years prior to the signature of informed consent.
19. Major surgery or interventional therapy was performed within 4 weeks prior to the first dose and did not fully recovered (except tumor biopsy and puncture).
20. For Phase II subjects:

* Received an immune checkpoint inhibitor (anti-PD-1/PD-L1/CTLA-4 antibody) or other immune checkpoint inhibitor therapy within 28 days prior to the first treatment with the test drug;
* Prior concurrent receipt of antitumor agents targeting VEGF/VEGFR and PD-1/PD-L1;
* Experienced permanent discontinuation of immunotherapy due to toxicity of immune checkpoint inhibitor therapy prior to receiving administration of study drug;
* Currently receiving anticoagulant medications (except for subjects on prophylactic doses of heparin).
21. A history of uncontrollable mental illness or subjects currently experiencing such conditions.
22. Subjects with poor compliance who are expected to be unable to complete the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RemeGen Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tianshu Liu, ph.D

Role: PRINCIPAL_INVESTIGATOR

Shanghai Zhongshan Hospital

Locations

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Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status RECRUITING

Gansu Wuwei Tumour Hospital

Wuwei, Gansu, China

Site Status RECRUITING

Meizhou People's Hospital

Meizhou, Guangdong, China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status RECRUITING

Nanyang Central Hospital

Nanyang, Henan, China

Site Status RECRUITING

Xinyang Central Hospital

Xinyang, Henan, China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

Site Status RECRUITING

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Shandong, China

Site Status RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, China

Site Status RECRUITING

Changzhi People's Hospital

Changzhi, Shanxi, China

Site Status RECRUITING

West China Hospital Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

The Second People's Hospital of Neijiang

Neijiang, Sichuan, China

Site Status RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status RECRUITING

Zhongshan Hospital Fudan University

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xiaohong Su

Role: CONTACT

+8610-65018841

Tianshu Liu, ph.D

Role: CONTACT

+86-21-31587871

Facility Contacts

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Tianshu Liu, ph.D

Role: primary

+86-21-31587871

Other Identifiers

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RC118-C002

Identifier Type: -

Identifier Source: org_study_id

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