Clinical trial NCT04679038: A Trial of SHR-1701 in Combination With Famitinib in Patients With Advanced Solid Tumors
Official title: SHR-1701 Plus Famitinib Malate in Advanced Solid Tumors: An Open-label, Multi-center, Phase I/II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: SHR-1701 plus famitinib
Primary purpose: TREATMENT

Brief summary: This is an open-label, multi-center study to evaluate the efficacy and safety of SHR-1701 in combination with famitinib in subjects with metastatic or locally advanced solid tumor. There are two parts of the study: combinational therapy part and monotherapy part. Phase I of combinational therapy part is to determine the recommended dose for Phase II (RP2D) for famitinib in the combined regimen, then efficacy and safety of SHR-1701 plus famitinib (RP2D) will be further evaluated in the following Phase II in cohorts 1/2/3, with simon's two-stage design. Meanwhile, efficacy and safety of famitinib will also be assessed in cohorts 4/5 in the monotherapy part.


Eligibility criteria: Inclusion Criteria:

1. Phase I of combinational therapy part: Histologically proven metastatic or locally advanced solid tumors, for which no effective standard treatment exists or standard therapy has failed.
2. Phase II of combinational therapy part and monotherapy part: Histologically confirmed metastatic or locally advanced selected solid tumor types with 0-2 prior lines of systemic therapy.

   For cohorts 1 or 4, patients with biliary tract carcinoma failed to one prior systemic treatment. Patients with previous adjuvant/neo-adjuvant therapy completed within 6 months can be enrolled.

   For cohort 2, patients with clear-cell renal cell carcinoma (or predominantly clear-cell subtype with primary tumor resected) after failure of no more than first-line standard therapy; For cohorts 3 or 5, patients with hepatocellular carcinoma must have progressed on prior first- or second-line standard therapy; Child-Pugh Class A; BCLC stage B or C, and not suitable for surgical or local therapy.
3. Subjects are 18 years old or older when signing the informed consent and gender is not limited.
4. Life expectancy of at least 12 weeks.
5. Eastern Cooperative Group (ECOG) performance status of 0 to 1.
6. At least one measurable lesion according to RECIST version 1.1.
7. Tumor tissue must be available for biomarker analysis prior to the first dose of treatment, If not available, subjects can consult the investigator for enrollment agreement.
8. Adequate hematological, hepatic and renal function as defined in the protocol.
9. Subjects with HBV infection: HBV DNA\<500 IU/mL or \< 2500 copy/mL, must receive anti-HBV therapy.
10. Subjects with HCV-RNA(+) must receive antiviral therapy.
11. Able and willing to provide signed informed consent form, and able to comply with all procedures.

Other protocol defined inclusion criteria could apply.

Exclusion Criteria:

1. For cohorts 1 or 4: known ampullary cancer or mixed cancer (HCC-ICC).
2. For cohorts 3 or 5: known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; history of hepatic encephalopathy.
3. For subjects in combinational therapy part: prior treatment with any anti-PD-1/PD-L1, or anti-CTLA-4 agents (specifically targeting T-cell co-stimulation or checkpoint pathways), or TGF-β inhibitors.
4. For cohort 4: prior treatment with VEGFR directed therapies including famitinib.
5. Factors to affect oral administration.
6. Major surgery procedure within 28 days prior to the first dose of trial treatment (excluding prior diagnostic biopsy or PICC); anticancer treatment within 28 days before the first dose of trial treatment; subjects in combinational therapy part who have received systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment should also be excluded.
7. Moderate-to-severe ascites with clinical symptoms.
8. Active or history of central nervous system metastases.
9. Known genetic or acquired hemorrhage or thrombotic tendency.
10. History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal haemorrhage.

Other protocol defined exclusion criteria could apply.

Primary outcomes:
measure: RP2D
timeFrame: First cycle (21 days)
measure: Objective response rate (ORR)
timeFrame: up to approximately 3 years (anticipated)
Secondary outcomes:
measure: Clinically Significant Toxicity
timeFrame: First cycle (21 days)
measure: AEs+SAEs
timeFrame: up to approximately 3 years (anticipated)
measure: DCR
timeFrame: up to approximately 3 years (anticipated)
measure: DoR
timeFrame: up to approximately 3 years (anticipated)
measure: PFS
timeFrame: up to approximately 3 years (anticipated)
measure: OS
timeFrame: up to approximately 3 years (anticipated)
measure: 6-month OS rate
timeFrame: From the start of treatment to 6 months
measure: 12-month-OS rate
timeFrame: From the start of treatment to 12 months
measure: Cmax of SHR-1701
timeFrame: up to approximately 3 years (anticipated)
measure: C6h of Famitinib
timeFrame: up to approximately 6 months (anticipated)
measure: Cmax,ss
timeFrame: up to approximately 3 years (anticipated)
measure: AUC0-24h,ss
timeFrame: up to approximately 3 years (anticipated)]
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The 2nd Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: General Hospital of Eastern Theater Command
state: Jiangsu
city: Gannan
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital,Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Tianjin
country: China
facility: The 2nd Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: The 1st Affiliated Hospital of Zhejiang Medical University
state: Zhejiang
Study officials:
References: