A Study of RC118 in Patients with Locally Advanced Unresectable or Metastatic Malignant Solid Tumors

NCT05205850 | Recruiting Phase 1

• 1 other identifier: RC118-C001
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 2

Brief Summary

In Phase I, This study will explore the tolerability and safety of RC118 in patients with locally advanced unresectable or metastatic malignant solid tumors with positive Claudin 18.2 expression, and determine the maximum tolerated dose (MTD) and the recommended dose in phase II clinical trials (RP2D); In Phase IIa, to explore the clinical effectiveness and safety of long-term use of RC118 at RP2D doses for patients with different tumor types。

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT)

  In the DLT evaluation window (observation period 1-28 days after the first administration), according to the NCI-CTCAE v5.0 grading standard, the investigator or the sponsor believes that toxic reaction which are reasonably related to RC118 treatment

  28 days after first treatment.

• The incidence and severity of adverse events (AE)

  Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0

  From the day of ICF sign to 28 days after the day of the last treatment

• Objective response rate (ORR)

  Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

  15 months

Secondary Outcomes (6)

• Disease Control Rate (DCR)

  15 months

• Progression-free survival (PFS)

  15 months

• Duration of Remission (DOR)

  15 months

• Pharmacokinetic index

  15 months

• Immunogenicity

  15 months

Study Arms (1)

RC118-ADC

EXPERIMENTAL

Participants will be allocated to one of the following dose groups: 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0mg/kg, and receive a treatment of RC118-ADC followed by 14 days of dose limited toxicity (DLT) observation period.

Drug: RC118-ADC

Interventions

RC118-ADC DRUG

RC118 for injection is a novel antibody-drug conjugate, with a Claudin 18.2-targeting antibody and a microtube inhibitor

Also known as: RC118 for injection

RC118-ADC

Eligibility Criteria

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

You may qualify if:

• Volunteer to participate in this study and sign written informed consent
• years old ≤ age ≤ 75 years old, no gender limit
• ECOG physical status score is 0 or 1 point
• The expected survival time exceeds 12 weeks
• Standard treatment is ineffective (disease progression or no remission after treatment), patients who cannot tolerate standard treatment, locally advanced unresectable or metastatic malignant solid tumors
• The subject agrees to provide freshly collected tumor tissue specimens or collected and preserved tumor tissue specimens within 2 years during the screening period for CLDN 18.2 testing, and must meet the following criteria： A.Phase I dose escalation stage/dose confirmation stage: patients with gastric cancer, esophageal cancer, gastroesophageal junction cancer, pancreatic cancer, ovarian cancer, and cholangiocarcinoma with positive Claudin 18.2 expression (membrane staining is observed in any tumor cells); B.Phase IIa Dose Expansion phase: (positive membrane staining observed in any tumour cell) patients with gastric/gastro-oesophageal adenocarcinoma, pancreatic cancer; C. Phase IIa dose-optimisation phase: patients with gastric/gastro-oesophageal adenocarcinoma with Claudin 18.2-positive (positive membrane staining observed in any tumour cell)
• According to the RECIST v1.1 standard, based on imaging examination (CT/MRI), there is at least one measurable or evaluable target lesion
• Sufficient bone marrow, liver, and kidney functions (subject to the normal value of the clinical trial center): absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet ≥ 100×109/L, hemoglobin ≥ 90 g/ L, serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN), ALT, AST or ALP ≤ 3 times ULN without liver metastasis; ALT, AST or ALP ≤ 5 times ULN with liver metastasis, serum creatinine ≤ 1.5 Times ULN, International Normalized Ratio (INR) ≤ 1.5 times ULN, APTT ≤ 1.5 times ULN
• Male or female subjects with fertility must agree to take effective contraceptive measures during the study period and within 6 months after the end of the last medication, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine

You may not qualify if:

• Women who are pregnant or breastfeeding, or women whose blood pregnancy test results are positive during the screening period (female subjects who are infertile do not need to undergo a pregnancy test, such as hysterectomy and/or bilateral ovaries in the past Women with resection or amenorrhea ≥12 months)
• Subjects with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), and human immunodeficiency virus antibody (HIV-Ab) during the screening period
• Subjects with a prior history of other acquired, congenital immunodeficiency diseases; subjects who are preparing for or have previously undergone organ or bone marrow transplantation;
• Those who have previously received targeted therapy drugs for Claudin 18.2; or participated in clinical trials of other drugs within 4 weeks before the first administration and received trial drugs
• Have vaccinated within 4 weeks before the first dose or plan to vaccinate any vaccine during the study period
• Allergic to known research drug ingredients or excipients
• Combined use of vitamin K antagonist anticoagulant drugs; combined use of therapeutic doses of heparin (subjects using preventive doses of heparin can be included in the study)
• Received anti-tumor therapy (surgery, chemotherapy, radiotherapy, biological therapy) within 4 weeks before the first administration, and received palliative radiotherapy for bone metastases within 2 weeks
• The toxicity of previous anti-tumor treatments has not returned to the level 0 or 1 of NCI-CTCAE v5.0 (except for hair loss)
• There are clinical symptoms of pleural fluid, ascites, and pericardial effusions require drainage (patients who do not require drainage or whose drainage is discontinued and who do not have a significant increase in effusion within 5 days may be included in the study)
• According to the judgment of the investigator, an active infection with clinical significance
• Combined with other diseases that seriously endanger the safety of the subject or affect the completion of the test, such as gastrointestinal bleeding (within 4 weeks before the first dose), peptic ulcer, intestinal obstruction, intestinal paralysis, interstitial pneumonia, lung Fibrosis, kidney failure, and uncontrolled diabetes
• QTc interval during the screening period\>480 ms (based on the average of 3 screening electrocardiograms); previous family or personal history of long/short QT interval syndrome; ventricular arrhythmia deemed clinically significant by the investigator Medical history, or currently receiving antiarrhythmic drug treatment, or implantation of arrhythmia defibrillation device
• Past myocardial infarction (within 6 months before the first administration), severe or unstable angina, coronary or peripheral artery bypass grafting, New York Heart Association (NYHA) grade 3\~4 heart failure, no Controlled hypertension
• People who have had alcohol dependence or drug abuse in the past

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (2)

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

The first affiliated hospital, zhejiang universtity school of medicine

Hangzhou, Zhejiang, 310009, China

NOT YET RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tianshu Liu, ph.D

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianming Fang, ph.D

CONTACT

+8610-58075763; jianmingfang@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: January 25, 2022
• Study Start: March 3, 2022
• Primary Completion: September 30, 2025
• Study Completion: December 1, 2025
• Last Updated: January 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)