Clinical trial NCT04617314: A Study of RC108-ADC in Subjects With Advanced Malignant Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: c-Met positive
solid tumor
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: From the day of ICF signment to 28 days after the day of the last treatment
measure: Maximum Tolerated dose of RC108
timeFrame: 21 days after first treatment.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax)
timeFrame: 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.
measure: PK parameter for TAb: Time to maximum concentration (Tmax)
timeFrame: 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.
measure: PK parameter for TAb: Area under the concentration-time curve (AUC)
timeFrame: 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.
measure: PK parameter for TAb: Trough concentration (Ctrough)
timeFrame: 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.
measure: PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
timeFrame: 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.
measure: PK parameter for TAb: Systemic clearance (CL)
timeFrame: 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.
measure: PK parameter for antibody-drug conjugate (ADC): Cmax
timeFrame: 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.
measure: PK parameter for ADC: Tmax
timeFrame: 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.
measure: PK parameter for ADC: AUC
timeFrame: 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.
measure: PK parameter for ADC: Ctrough
timeFrame: 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.
measure: PK parameter for ADC: t1/2
timeFrame: 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.
measure: PK parameter for ADC: CL
timeFrame: 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.
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
timeFrame: 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.
measure: PK parameter for MMAE: Tmax
timeFrame: 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.
measure: PK parameter for MMAE: AUC
timeFrame: 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.
measure: PK parameter for MMAE: Ctrough
timeFrame: 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.
measure: PK parameter for MMAE: t1/2
timeFrame: 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.
measure: PK parameter for MMAE: CL
timeFrame: 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.
measure: Immunogenicity assessment
timeFrame: Dose 1 to Dose 3: pre-dose, and 504 hours after start of infusion (Dose 3 only)
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College
state: Beijing
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College
name: Yuankai Shi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: