A Study of RC148 As a Single Agent and Combination Therapy in Patients with Locally Advanced Unresectable or Metastatic Malignant Solid Tumors

NCT06016062 | Recruiting Phase 1

• 1 other identifier: RC148-C001
• Study Type: interventional
• Target: 221
• Locations: 1 country
• Sites: 31

Brief Summary

The primary objective of Phase I of this trial is to evaluate the safety, tolerability, maximum tolerated dose (MTD)/maximum administered dose (MAD) of RC148 in patients with locally advanced unresectable or metastatic solid tumors to determine the recommended Phase II dose (RP2D), and the secondary objective is to evaluate the PK and PD characteristics, immunogenicity and preliminary clinical efficacy of RC148. Phase II will primarily evaluate the efficacy of the RC148 combination regimen, and secondarily will assess safety and tolerability, PK characteristics, and immunogenicity. During the trial, investigators will also evaluate the potential correlation of biomarkers with efficacy.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (5)

• Phase I：Maximum tolerated dose (MTD)/Maximum administered dose (MAD)

  MTD/MAD based on number of Dose limiting toxicity (DLT)

  Subjects will be treated and observed for DLT through the end of the first cycle (Days 1-28)

• Phase I：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 RC148 treatment

  28 days after first treatment

• Phase I：The incidence and severity of adverse events (AE)

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

  From the day of ICF sign to 28/90 days after the day of the last treatment

• Phase I：Recommended Phase 2 dose (RP2D)

  The RP2D may be selected as 1 dose level lower than the MTD and will be determined in discussion with the safety monitoring committee based on all available data

  28 days or 1cycle

• Phase II: ORR, DCR, DoR, PFS based on RECIST v1.1 investigator assessment;

  15 months

Secondary Outcomes (10)

• Phase I：Overall Response Rate (ORR)

  15 months

• Phase I：DCR

  15 months

• Phase I：DOR

  15 months

• Phase I：PFS

  15 months

• Phase I：Pharmacodynamic characterization of RC148

  15 months

Study Arms (8)

Phase1-RC148 monotherapy

EXPERIMENTAL

Participants will be allocated to one of the following dose groups:1.0, 3.0, 10.0, 20.0, and 30.0mg/kg, and receive a treatment of RC148 followed by 28 days of dose limited toxicity (DLT) observation period.

Drug: RC148 Monotherapy

Phase2-Arm1 (NSCLC): RC148+docetaxel

EXPERIMENTAL

RC148+docetaxel Combination Therapy： Participants receive RC148 (10mg/kg or 20mg/kg Q3W) in combination with docetaxel (75mg/m\^2 Q3W).

Drug: RC148+docetaxel Combination Therapy

Phase2-Arm 2 (Cervical): RC148+RC48

EXPERIMENTAL

RC148+RC48 Combination Therapy: Participants receive RC148 (20mg/kg Q2W) in combination with RC48 (2.0mg/kg Q2W).

Drug: RC148+RC48 Combination Therapy

Phase2-Arm 3 (Gastric cancer) : RC148+RC48

EXPERIMENTAL

RC148+RC48 Combination Therapy: Participants receive RC148 (20mg/kg Q2W) in combination with RC48 (2.0mg/kg Q2W).

Drug: RC148+RC48 Combination Therapy

Phase2-Arm 4 (Lung Adenocarcinoma): RC148+RC88

EXPERIMENTAL

RC148+RC88 Combination Therapy: Participants receive RC148 (20mg/kg Q3W) in combination with RC88 (2.0mg/kg Q3W).

Drug: RC148+RC88 Combination Therapy

Phase2-Arm 5 (Platinum-resistant Ovarian cancer) : RC148/Bevacizumab+RC88

EXPERIMENTAL

RC148+RC88 Combination Therapy: Participants receive RC148 (20mg/kg Q3W) in combination with RC88 (2.0mg/kg Q3W). Bevacizumab+RC88 Combination Therapy: Participants receive Bevacizumab (15mg/kg Q3W) in combination with RC88 (2.0mg/kg Q3W).

Drug: RC148/Bevacizumab+RC88 Combination Therapy

Phase2-Arm 6 (Platinum-sensitive Ovarian cancer): RC148+RC88

EXPERIMENTAL

RC148+RC88 Combination Therapy: Participants receive RC148 (20mg/kg Q3W) in combination with RC88 (2.0mg/kg Q3W).

Drug: RC148+RC88 Combination Therapy

Phase2-Arm 7 (MSLN-expressing Cervical cancer): RC148+RC88

EXPERIMENTAL

RC148+RC88 Combination Therapy: Participants receive RC148 (20mg/kg Q3W) in combination with RC88 (2.0mg/kg Q3W).

Drug: RC148+RC88 Combination Therapy

Interventions

RC148 Monotherapy DRUG

RC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle

Also known as: RC148 for injection

Phase1-RC148 monotherapy

RC148+docetaxel Combination Therapy DRUG

RC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle； Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.

Phase2-Arm1 (NSCLC): RC148+docetaxel

RC148+RC48 Combination Therapy DRUG

RC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle； RC48 will be administered as an IV infusion on Day 1 of each 2-week cycle.

Phase2-Arm 2 (Cervical): RC148+RC48; Phase2-Arm 3 (Gastric cancer) : RC148+RC48

RC148+RC88 Combination Therapy DRUG

RC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle； RC88 will be administered as an IV infusion on Day 1 of each 3-week cycle.

Phase2-Arm 4 (Lung Adenocarcinoma): RC148+RC88; Phase2-Arm 6 (Platinum-sensitive Ovarian cancer): RC148+RC88; Phase2-Arm 7 (MSLN-expressing Cervical cancer): RC148+RC88

RC148/Bevacizumab+RC88 Combination Therapy DRUG

RC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle; RC88 will be administered as an IV infusion on Day 1 of each 3-week cycle; Bevacizumab will be administered as an IV infusion on Day 1 of each 3-week cycle

Phase2-Arm 5 (Platinum-resistant Ovarian cancer) : RC148/Bevacizumab+RC88

Eligibility Criteria

• Age: 18 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 years (phase Ⅰ), 18 to 75 years old (Including 18 and 75 years, phase Ⅱ).
• Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Projected life expectancy of at least 12 weeks.
• At least one measurable target lesion based on imaging according to RECIST v1.1 criteria (For patients who have received prior radiotherapy, radiotherapy-treated lesions may be considered as target lesions if the lesion is measurable according to RECIST v1.1 criteria and there is evidence of significant progression after radiotherapy.);
• Phase I (RC148 monotherapy): Patients with locally advanced unresectable or metastatic malignant solid tumors whose disease has progressed with standard therapy, or who are unable to tolerate standard therapy, or in whom the subject refuses standard therapy;
• Phase II (Combination Therapies):
• Cohort 1 (non-small cell lung cancer): Patients with locally advanced unresectable or metastatic malignant solid tumors with disease progression on standard therapy, or intolerance of standard therapy, or refusal of standard therapy.
• Cohort 2 (HER2-expressing cervical cancer): Subjects with advanced non-small cell lung cancer diagnosed by histological or cytological examination, locally advanced or metastatic, with AGA- confirmed by prior genetic testing, who have received a PD-1/PD-L1 inhibitor and platinum-based chemotherapy as a first or second-line advanced treatment, and who have not received docetaxel chemotherapy.
• Cohort 3 (HER2 expressing gastric cancer): Histologically and/or cytologically confirmed locally advanced or metastatic gastric adenocarcinoma (including gastroesophageal junction adenocarcinoma) with HER2 expression (IHC ≥1+). Subjects who have progressed or are intolerant to standard first-line therapy only (PD-1/PD-L1 inhibitor + platinum-containing chemotherapy ± trastuzumab, and not including paclitaxel). Disease progression during neoadjuvant therapy and within 6 months of the end of adjuvant therapy will also be considered a failure of first-line therapy.
• Cohort 4 (MSLN-expressing lung adenocarcinoma): Histologically or cytologically confirmed lung adenocarcinoma without other pathologic components; driver gene negative, MSLN-expressing (IHC ≥1+) advanced lung adenocarcinoma subjects who have received PD-1/PD-L1 inhibitor and platinum-based chemotherapy (combination or sequential) and have not received paclitaxel-based chemotherapy.
• Cohort 5 (platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer): pathologic type needs to be high-grade serous ovarian cancer; Subjects who have progressed on prior 1-4 lines of antitumor therapies; Definition of platinum-resistance: 1) Patients who have received 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR), and then progressed between \>3 months and ≤6 months after the date of the last platinum; 2) Patients who have received 2 or 3 lines of platinum-based therapies must have received at least 4 cycles of platinum and have progressed on or within 6 months after the last dose of platinum.
• Cohort 6 (platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer): Pathological type needs to be high-grade serous EOC; Subjects who have received 1-4 lines of prior antitumor therapies were included.
• Cohort 7 (MSLN-expressing cervical cancer): Subjects with recurrent or metastatic cervical cancer expressing mesothelin (MSLN) (IHC ≥1+) that is histologically confirmed, ineligible for surgery or radiotherapy, and has progressed after at least 1L of platinum-based chemotherapy.
• Participants agree to provide pre-treatment archived/biopsied tumor samples for biomarker-related testing such as retrospective programmed cell death protein 1 (PD-L1) expression levels. Biopsies will be considered at screening only if archived samples are not available. Fresh tumor biopsies will not be considered if significant risk procedures are required per the discretion of the Investigator.

You may not qualify if:

• Pregnant or lactating.
• Cohort 1 in Phase II, patients with histologically or cytologically confirmed non-small cell lung cancer, other than squamous lung cancer and lung adenocarcinoma, (including subjects with squamous or adenocarcinoma in combination with other pathologic types of non-small cell lung cancer;) prior treatment with docetaxel, or an antitumor agent that targets VEGF/VEGFR; and treatment with at least 2 cycles of an immune checkpoint inhibitor, with a best response of PD, or best response of CR/PR/SD with disease progression within 6 months of first dose.
• Cohorts 4-7 in Phase II, patients with ocular corneal conditions at screening such as congenital corneal dystrophy, meibomian gland dysfunction (MGD), viral keratitis (dendritic, map-like, corneal stromal keratitis), uveitis, corneal endothelial decompensation, glaucoma, iridocorneal endothelial syndrome (ICE).
• Subjects with active hepatitis B or C; human immunodeficiency virus (HIV)-positive subjects.
• Those who have received a live vaccine within 28 days prior to the first RC148 administration or who plan to receive any live vaccine during the study period.
• Participant with a history of other acquired/congenital immunodeficiency diseases or organ transplantation.
• Active autoimmune disease requiring systemic therapy, such as systemic lupus erythematosus, psoriasis requiring systemic therapy, or rheumatoid arthritis, within the past 2 years; however, alternative therapies are not considered systemic therapies and are permitted for use and enrollment.
• Subject has received an immune checkpoint inhibitor (anti-PD-1/PD-L1/CTLA-4 antibody) or other immune checkpoint inhibitor therapy within 28 days prior to initiation of treatment with the study drug or has experienced permanent discontinuation of immunotherapy due to toxicity of immune checkpoint inhibitor therapy prior to receiving administration of the study drug.
• Subjects who have participated in a clinical trial of another drug and received the test drug within 4 weeks prior to the first dose of RC148.
• Prior concomitant treatment with antitumor agents targeting VEGF/VEGFR and PD-1/PD-L1 (except for subjects with cervical cancer). For cohorts 2-3 in Part 2, subjects with prior antibody-drug conjugates treatment. For cohorts 4-7 in Part 2, subjects with prior antibody-drug conjugates and MSLN-targeting drugs.
• Known hypersensitivity or delayed hypersensitivity to certain components of the study drug or to similar drugs.
• Participant who are under the treatment of anticoagulant drugs. Participants using prophylactic doses of heparin are eligible in the study.
• Subject received last systemic antitumor therapy, including surgery, chemotherapy, radiotherapy, and biologic therapy within 4 weeks prior to the first study drug administration; received small molecule tyrosine kinase inhibitor therapy or immunotherapy within 2 weeks prior to the first drug administration; or received herbal therapy for antitumor indications within 1 week prior to the first drug administration or received bone/other solitary metastases within 2 weeks prior to the first study drug administration Palliative radiotherapy.
• Previous adverse reactions resulting from previous anti-tumour therapies, which have not returned to Grade 1 according to NCI-CTCAE v5.0 at screening.
• Presence of grade ≥2 sensory or motor neuropathy.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (31)

Anhui Provincial Hospital

Anhui, China

RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, China

RECRUITING

Beijing University Cancer Hospital

Beijing, China

RECRUITING

The Fifth Medical Center of Chinese PLA General Hospital

Beijing, China

RECRUITING

Jilin Cancer Hospital

Changchun, China

RECRUITING

Hunan Cancer Hospital

Changsha, China

RECRUITING

Hunan Second People's Hospital

Changsha, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, China

RECRUITING

Chongqing University Cancer Hospital

Chongqing, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

The Second Affiliated Hospital of Guilin Medical University

Guilin, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, China

RECRUITING

Jinan Central Hospital

Jinan, China

RECRUITING

Qilu Hospital of shangdong university

Jinan, China

RECRUITING

Shandong Cancer Hospital

Jinan, China

RECRUITING

Meizhou People's Hospital

Meizhou, China

RECRUITING

Guangxi Medical University Cancer Hospital & Guangxi Cancer Institute

Nanning, China

RECRUITING

Nanyang City Center Hospital

Nanyang, China

RECRUITING

Nanyang Second General Hospital

Nanyang, China

RECRUITING

Shanghai Pulmonology Hospital

Shanghai, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, China

RECRUITING

Shengjing Hospital of China Medical University

Shenyang, China

RECRUITING

Shanxi Provincial Tumor Hospital

Taiyuan, China

RECRUITING

Tongji Hospital, Tongji Medical College of HUST, China

Wuhan, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

Wuhan, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

RECRUITING

Yunnan Cancer Hospital

Yunnan, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jianmin Fang, Ph.D

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Jianming Fang, ph.D

CONTACT

+8610-58075763; jianmingfang@hotmail.com

Study Design

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

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 29, 2023
• Study Start: September 14, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (31)