Trial Title:
A Study of RC148 in Patients With Locally Advanced Unresectable or Metastatic Malignant Solid Tumors
NCT ID:
NCT06016062
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RC148
Description:
RC148 is a bispecific antibody, targeting programmed death-1(PD-1) and Vascular
endothelial growth factor(VEGF).
Arm group label:
RC148
Other name:
RC148 for injection
Summary:
This trial is to evaluate the safety, tolerability, maximum tolerated dose (MTD) /
maximum administered dose (MAD), pharmacokinetics (PK), pharmacodynamics, immunogenicity
and recommended Phase 2 dose (RP2D) of RC148 in participants with locally advanced
unresectable or metastatic solid tumors.In addition, the preliminary anti-tumour efficacy
of RC148 as single agent will be assessed.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participant must be able to provide documented voluntary informed consent.
2. Male or female participants ≥ 18 years.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
4. The expected survival period exceeds 12 weeks.
5. At least one target lesion that can be measured per Response Evaluation Criteria in
Solid Tumours (RECIST) v1.1.(For patients with prior radiotherapy,
radiotherapy-treated lesions may be considered target lesions if they are measurable
according to RECIST v1.1 criteria and there is evidence of significant progression
after radiotherapy)
6. Histologically or cytologically documented advanced or metastatic solid tumor that
is refractory/relapsed to standard therapies, or for which no effective standard
therapy is available, or the subject refuses standard therapy.
7. Participants agree to provide pre-treatment archived /biopsy tumour samples (8-10
tissue slides) for retrospective programmed cell death protein 1 (PD-1)Expression
level and MSI/MMR status related tests.Tumor specimen for marker detection should be
from the most recent timepoint before entering the trial. Only when archived samples
cannot be obtained, the biopsy will be considered at screening. Fresh tumour
biopsies will NOT be considered if significant risk procedures are required per the
discretion of the Investigator.
8. Adequate bone marrow, liver, and renal function defined as:
- absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L,
- platelet ≥ 100 × 10^9/L,
- haemoglobin ≥ 90 g/L,
- serum total bilirubin ≤ 1.5 × upper limit of normal (ULN),
- ALT, AST ≤ 2.5 × ULN (≤ 5 × ULN when there is known liver metastasis),
- serum creatinine ≤ 1.5 × ULN,
- International normalized ratio (INR) ≤ 1.5 × ULN,
- Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. Urinalysis results
for urinary protein <++; Subjects for whom urine protein ≥++ by urine test
strip at baseline A 24-hour urine collection should be performed and the amount
of protein in the urine over a 24-hour period should be <1g;
9. 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 contraceptive device.
Exclusion Criteria:
1. Pregnant or lactating.
2. Diagnosed active hepatitis B infection (defined as positive of hepatitis B surface
antigen (HBsAg) and hepatitis B deoxyribonucleic acid [DNA]≥500IU/ml), active
hepatitis C infection (defined as presence of hepatitis C ribonucleic acid [RNA]),
and human immunodeficiency virus (HIV) infection (defined as positive HIV test)
during the screening period.
3. Received live attenuated vaccination within 28 days prior to the first dose of RC148
4. Participant with a history of other acquired/congenital immunodeficiency diseases or
organ transplantation.
5. Participant who received prior anti-PD-1, anti- programmed cell death protein ligand
1 (anti-PD-L1), anti-cytotoxic T lymphocyte-associated (CTLA)-4 or any other
immunotherapy or immune-oncology agent within 28 days of commencing treatment with
RC148 or experienced a toxicity that led to permanent discontinuation of prior
immunotherapy.
6. Participant who had participated in other clinical trials and received study drug
within 4 weeks before the first administration of IP.
7. Allergic constitution or allergic to known research drug active ingredients or
excipient.
8. Participant who are under the treatment of anticoagulant drugs (e.g., warfarin,
apixaban, and heparin). Participants using prophylactic doses of heparin (e.g.,
low-molecular-weight heparins [LMWH]) are eligible in the study.
9. Participant undergo any anti-tumour therapy, including surgery, chemotherapy,
radiotherapy and biological therapy within 4 weeks prior to the first administration
of IP,or Chinese traditional medicine for an antitumor indication within 2 weeks
prior to first drug administration, or palliative radiotherapy for bone/other
solitary metastases within 2 weeks prior to the first administration of IP.
10. Previous adverse reactions resulting from previous anti-tumour therapies, which have
not returned to Grade 0 or 1 according to NCI-CTCAE v5.0 (except alopecia) at
screening.
11. There are clinical symptoms of fluid in the third space (e.g., large amounts of
pleural fluid or ascites).
12. A clinically significant active infection judged by the investigator(IP begins 2
weeks after completion of anti-infective treatment).
13. Comorbidities that may seriously endanger the participant's safety or affect the
completion of the study, such as gastrointestinal bleeding (within 4 weeks prior to
the screening period), History of hemoptysis (single hemoptysis > 2.5 mL of bright
red blood) within 4 weeks prior to screening，peptic ulcer (within 4 weeks prior to
the screening period), intestinal obstruction, intestinal paralysis, interstitial
pneumonia, pulmonary fibrosis, kidney failure,Severe esophagogastric fundic varices
and uncontrolled diabetes.
14. QT interval corrected by Fridericia's formula (QTcF) interval > 450 ms( male） and
(QTcF) interval > 470 ms（ femal (based on the mean value of the triplicate screening
electrocardiogram [ECG]); family or personal history of long/short QT syndrome;
history of ventricular arrhythmia deemed clinically significant by the investigator,
or currently receiving antiarrhythmic drug treatment, or implantation of arrhythmia
defibrillation device.
15. Have experienced arterial/venous thromboembolic events, such as cerebrovascular
accident (including transient ischemic attack), deep vein thrombosis and pulmonary
embolism within 1 year prior to the initiation of study treatment;
16. History of myocardial infarction within 6 months prior to the screening period,
severe or unstable angina pectoris, coronary or peripheral artery bypass grafting,
heart failure ≥ 3 (New York Heart Association), or uncontrolled hypertension.
17. Participants with a condition requiring systemic treatment with either
corticosteroid (> 10 mg daily) or other immunosuppressive medications within 2 weeks
of first IP administration.
18. Participants with active central nervous system (CNS) metastases. Participants with
treated CNS metastases are permitted on study if the CNS metastases have been
clinically stable for at least 4 weeks prior to treatment initiation and baseline
scans show no evidence of new or enlarged lesions and meanwhile participant does not
have leptomeningeal disease.For Carcinomatous Meningitis, regardless of whether the
clinical status is stable or not, they should be excluded;
19. Have undergone major surgeries within 4 weeks prior to study treatment and have not
recovered yet;
20. History or presence of uncontrolled mental illness at the discretion of the
Investigator, which may place the participant at increased risk of
safety/tolerability issues.
21. The participant is, in the opinion of the investigator, expected to be non-compliant
with critical trial procedures and is not willing or able to adhere to the trial
requirements in the future.
22. Participants who are not appropriate for this clinical trial at the discretion of
the investigator.
23. Previously received dual anti-tumor drugs targeting both VEGF/VEGFR and PD-1/PD-L1.
tumor drugs;
24. Screening stage imaging shows tumor invasion of large blood vessels.
25. Other malignancies within 5 years prior to the start of study dosing, except:
malignancies that are expected to resolve with treatment (including, but not limited
to, adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous
cell skin cancer, or ductal carcinoma in situ of the breast treated by radical
surgery)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Suxia Luo
Investigator:
Last name:
Suxia Luo
Email:
Principal Investigator
Facility:
Name:
Shandong Tumor Hospital
Address:
City:
Jinan
Zip:
250117
Country:
China
Status:
Recruiting
Contact:
Last name:
Jinming Yu, ph.D
Phone:
0531-67626971
Investigator:
Last name:
Jinming Yu, ph.D
Email:
Principal Investigator
Facility:
Name:
Jinan Central Hospital
Address:
City:
Jinan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Meili Sun
Investigator:
Last name:
Meili Sun
Email:
Principal Investigator
Facility:
Name:
Qilu Hospital of shangdong university
Address:
City:
Jinan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Kun Song, M.D
Start date:
September 14, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
RemeGen Co., Ltd.
Agency class:
Industry
Source:
RemeGen Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06016062
