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

NCT06038396 | Recruiting Phase 1

• 1 other identifier: RC118-C002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• Phase1: Dose limiting toxicity (DLT)

  Toxicity occurs within the DLT evaluation window (1-21 days after the first dose) that the investigator or sponsor believes to be reasonably associated with RC118 or Toripalimab according to NCI-CTCAE v5.0.

  The first 3 weeks (21 days) after the start of dosing at each dose level

• Phase1/2: Adverse events (AEs)

  Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.

  [Time Frame: 15 months]

• Phase1: Maximum tolerated dose(MTD)

  Maximum tolerated dose(MTD)

  up to 12 months

• Phase1: Recommended Phase 2 Dose (RP2D)

  Recommended Phase 2 Dose (RP2D)

  up to 12 months

• Phase 2: Objective response rate (ORR)

  The proportion of patients whose BOR is a confirmed CR or PR. Tumor response will be evaluated using RECIST v.1.1.

  15 months

Secondary Outcomes (7)

• Disease Control Rate (DCR)

  15 months

• Progression-free survival (PFS)

  15 months

• Duration of Remission (DOR)

  15 months

• Overall survival (OS)

  15 months

• Phase 1: Objective response rate (ORR)

  15 months

Study Arms (2)

Part A-RC118 plus Toripalimab

EXPERIMENTAL

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

Drug: RC118; Drug: Toripalimab

Part B-RC118 plus Toripalimab / RC148

EXPERIMENTAL

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

Drug: RC118; Drug: Toripalimab; Drug: RC148

Interventions

RC118 DRUG

Dose A or dose B, Q2W

Also known as: RC118 for injection

Part A-RC118 plus Toripalimab; Part B-RC118 plus Toripalimab / RC148

Toripalimab DRUG

Fixed dose, Q3W

Also known as: Toripalimab injection, JS001

Part A-RC118 plus Toripalimab; Part B-RC118 plus Toripalimab / RC148

RC148 DRUG

Fixed dose, Q3W Other Names: RC148 injection

Part B-RC118 plus Toripalimab / RC148

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to participate in the study voluntarily and willing to provide written informed consent.
• male or female 18 ≤ age ≤ 75 years old.
• Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• The expected survival ≥12 weeks.
• 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.
• Subjects who received ≤2 prior systemic therapies.
• 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.
• According to the RECIST v1.1, there is at least one measurable target lesion.
• Sufficient heart, bone marrow, liver and kidney functions.
• 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.

You may not qualify if:

• 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).
• 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.
• Subjects with a history of other acquired or congenital immunodeficiency diseases, or who have undergone organ or bone marrow transplantation.
• 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.
• Have vaccinated within 4 weeks prior to the first dose or plan to receive any live vaccine during the study.
• Subjects are atallergic to the ingredients or excipients of the experimental drug.
• 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.
• 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).
• The clinical symptoms of pleural effusion, abdominal effusion, or pericardial effusion that requires drainage.
• Active infection within 2 weeks prior to the first dose that requires systemic anti-inflammatory therapy.
• 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%).
• The tumor lesion has a bleeding tendency or has received blood transfusion treatment within 4 weeks prior to the first dose.
• 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.
• 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.
• Experienced an arterial/venous thromboembolic event within 6 months prior to the study.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (18)

Fujian Cancer Hospital

Fuzhou, Fujian, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

RECRUITING

Gansu Wuwei Tumour Hospital

Wuwei, Gansu, China

RECRUITING

Meizhou People's Hospital

Meizhou, Guangdong, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

RECRUITING

Nanyang Central Hospital

Nanyang, Henan, China

RECRUITING

Xinyang Central Hospital

Xinyang, Henan, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

RECRUITING

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Shandong, China

RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, China

RECRUITING

Changzhi People's Hospital

Changzhi, Shanxi, China

RECRUITING

West China Hospital Sichuan University

Chengdu, Sichuan, China

RECRUITING

The Second People's Hospital of Neijiang

Neijiang, Sichuan, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

RECRUITING

Zhongshan Hospital Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Interventions

Injections; toripalimab

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tianshu Liu, ph.D

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaohong Su

CONTACT

+8610-65018841; na.su@remegen.com

Tianshu Liu, ph.D

CONTACT

+86-21-31587871; liu.tianshu@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 14, 2023
• Study Start: August 3, 2023
• Primary Completion: February 28, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 29, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)