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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04617314
• Other study ID #: RC108-C001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 10, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: RemeGen Co., Ltd.
• Contact: Xiaohong Su, M.D.
• Phone: +0810-65391479
• Email: xiaohong.su[@]remegen.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• RC108
RC108 for injection is a novel antibody-drug conjugate, with a c-Met-targeting antibody and a microtube inhibitor.

Locations

Country	Name	City	State
China	National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
RemeGen Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Immunogenicity assessment	Assessment of anti-RC108 antibodies	Dose 1 to Dose 3: pre-dose, and 504 hours after start of infusion (Dose 3 only)