A Phase I /IIa Study of RC88-ADC in Subjects With Advanced Malignant Solid Tumors

NCT04175847 | Completed Phase 1

• 1 other identifier: RC88-C001
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 4

Brief Summary

This was a multicenter, open, multi-cohort extended PHASE I/IIa study, consisting of 2 phases:Phase I (Phase I dose escalation) and Phase II (Phase IIa multi-cohort extension). The objective of this study was to evaluate safety, tolerability, pharmacokinetic characteristics, and initial efficacy in malignant pleural mesothelioma and MSLN in advanced malignant solid tumors.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Phase 1 Adverse events

  Adverse events was assessed by investigator(s) according to NCI-CTCAE v4.03

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

• Phase 1 Maximum Tolerated dose of RC88

  The dose level in which \>= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level.

  21 days after first treatment.

• Phase2

  ORR is evaluated by IRC

  24 weeks

Secondary Outcomes (21)

• Phase 1 Objective Response Rate (ORR)

  24 months

• Phase 1 Progression Free Survival (PFS)

  24 months

• Phase 1 and Phase2 Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax)

  Phase 1:Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hour (hr), 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose.Phase2 （Whole test cycle）

• Phase 1 and Phase2 PK parameter for TAb: Time to maximum concentration (Tmax)

  Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose.Phase2 （Whole test cycle）

• Phase 1 PK parameter for TAb: Area under the concentration-time curve (AUC)

  Cycle 1 and Cycle 3 (each cycle is 21 days): pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs, 168 hrs, 240 hrs (and 336 hrs) after start of infusion. Cycle 2: pre-dose.

Study Arms (1)

RC88

EXPERIMENTAL

Drug: RC88

Interventions

RC88 DRUG

Phase I:Participants will be allocated to one of the following dose groups: 0.1, 0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg, and receive a treatment of RC88-ADC followed by 21 days of dose limited toxicity (DLT) observation period. Phase IIa indication exploration

Also known as: RC88 for Injection

RC88

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary agreement to provide written informed consent.
• Age requirements ：phase I 18-70 (including 18 and 70) ,IIa ≥18 years old.
• Predicted survival ≥ 12 weeks.
• Phase I must be histologically or cytologically confirmed and have failed standard therapy (disease progression after treatment) or are intolerant, unable to receive, or nonexistent to standard care,Patients with partial advanced or metastatic malignant solid tumors;
• Phase II： Cohort 1：Advanced malignant mesothelioma； Cohort2：advanced ovarian carcinoma ；Cohort2 Other cancers that may benefit include pancreatic cancer, gastric adenocarcinoma, triple negative breast cancer, and lung adenocarcinoma
• Patients with malignant pleural mesothelioma were assessed using mRECIST criteria, and those with other cancers were assessed using RECIST V1.1 criteria.
• Mesothelin (MSLN) positive as confirmed by the central laboratory. Subject is able to provide specimens from primary or metastatic lesions for MSLN tests.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment:
• Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×10\^9 /L Platelets ≥ 100×10\^9 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN.
• All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• Use of investigational drug or device within 4 weeks prior to study dosing
• Known hypersensitivity to the components of RC88-ADC.
• Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia).
• Pericardial effusion or cardiac tamponade, or pleural or abdominal effusion with clinical symptoms that requires ongoing treatment.
• Has a history or current history of explosive, acute, chronic, recurrent or persistent myocarditis or pericarditis caused by any cause (eg, virus, tuberculosis, autoimmune disease, etc.)
• Ophthalmic screening is required: has a history of ocular lesions such as the cornea, limbus, conjunctiva, or eyelids (including but not limited to: corneal inflammation, corneal dystrophy, dry eye, meibomian gland dysfunction, uveitis, corneal endothelium Decompensation, glaucoma, iris corneal endothelial syndrome (ICE), etc.) can not be enrolled; has a ophthalmologists-confirmed current medical history of the cornea, limbus, conjunctiva, orbital lesions cannot be included;
• History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment.
• History of major surgery within 4 weeks of planned start of trial treatment.
• Has received live virus vaccine within 4 weeks prior to study administration or planned to receive live virus vaccine during study .
• Currently known active infection with HIV or tuberculosis.
• Diagnosed with HBsAg , HBcAb positive and HBV DNA copy positive, or HCVAb positive.
• Has Unstable angina, coronary angioplasty, stent implantation,Coronary artery bypass grafting, serious arrhythmias requiring treatment (e.g., persistent ventricular tachycardia, ventricular fibrillation,Torsional ventricular tachycardia), QTc \> 470 ms and long QT syndrome
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
• known central nervous system metastases.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (4)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Drum Tower Hospital

Nanjing, Jiangsu, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

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 22, 2019
• First Posted: November 25, 2019
• Study Start: April 14, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 7, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)