A Study of RC108-ADC in Subjects With Advanced Malignant Solid Tumors

A Phase I Study to Evaluate the Safety, Pharmacokinetics, and Effect of RC108-ADC For Injection in Subjects With c-Met Positive Advanced Malignant Solid Tumors

This study will evaluate the safety, pharmacokinetics, and effect of RC108-ADC for injeciton in subjects with c-Met positive advanced malignant solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: RC108

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary agreement to provide written informed consent.
2. Male or female, aged between 18 to 70 years.
3. Predicted survival for ≥ 12 weeks.
4. Diagnosed with histologically or cytologically confirmed locally advanced or metastatic solid tumors.
5. Measurable lesion according to RECIST 1.1.
6. c-Met positive as confirmed by the central laboratory. The subject is able to provide specimens from primary or metastatic lesions for c-Met tests.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
8. Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment:
9. Cardiac ejection fraction ≥ 50%. Median QTc < 450 ms. 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.
10. 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.
11. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

1. Known hypersensitivity to the components of RC108-ADC.
2. Toxicity of previous anti-tumor treatment not recovered to CTCAE (v5.0) Grade 0-1 (with exception of Grade 2 alopecia).
3. Uncontrolled pericardial effusion or cardiac tamponade, or pleural or abdominal effusion with clinical symptoms.
4. History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment.
5. History of major surgery within 4 weeks of planned start of trial treatment.
6. Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
7. Currently known active infection with HIV or tuberculosis.
8. Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.
9. 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.
10. 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.
11. Known central nervous system metastases.
12. Uncontrolled hypertension, diabetes, pulmonary fibrosis, acute lung disease, Interstitial lung disease, or liver cirrhosis;
13. Pregnancy or lactation.
14. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC108; Participants will be allocated to one of the following dose groups: 0.1, 0.3, 0.9, 1.5, 2.0, 2.5, and 3.0mg/kg, and receive a treatment of RC108-ADC followed by 21 days of dose limited toxicity (DLT) observation period.	Drug: RC108; RC108 for injection is a novel antibody-drug conjugate, with a c-Met-targeting antibody and a microtube inhibitor.; Other Names: RC108 for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Adverse events was assessed by investigator(s) according to NCI-CTCAE v4.03	From the day of ICF signment to 28 days after the day of the last treatment
Maximum Tolerated dose of RC108	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)	24 months
Progression Free Survival (PFS)	Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	24 months
Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax)	Cmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for TAb: Time to maximum concentration (Tmax)	Tmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for TAb: Area under the concentration-time curve (AUC)	AUC will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for TAb: Trough concentration (Ctrough)	Ctrough will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)	t1/2 will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for TAb: Systemic clearance (CL)	CL will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for antibody-drug conjugate (ADC): Cmax	Cmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for ADC: Tmax	Tmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for ADC: AUC	AUC will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for ADC: Ctrough	Ctrough will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for ADC: t1/2	t1/2 will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for ADC: CL	CL will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for Monomethyl Auristatin E (MMAE): Cmax	Cmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for MMAE: Tmax	Tmax will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for MMAE: AUC	AUC will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for MMAE: Ctrough	Ctrough will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for MMAE: t1/2	t1/2 will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
PK parameter for MMAE: CL	CL will be derived from the PK blood samples collected.	Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.
Immunogenicity assessment	Assessment of anti-RC108 antibodies	Dose 1 to Dose 3: pre-dose, and 504 hours after start of infusion (Dose 3 only)

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Principal Investigator: Yuankai Shi, M.D., Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: October 30, 2020
• First Submitted That Met QC Criteria: October 30, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Estimated): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: solid tumor; c-Met positive
• Additional Relevant MeSH Terms: Neoplasms; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: RC108-C001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No