A Trial of SHR-1701 in Combination With Famitinib in Patients With Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

SHR-1701 Plus Famitinib Malate in Advanced Solid Tumors: An Open-label, Multi-center, Phase I/II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04679038
• Other study ID #: SHR-1701-II-203
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 17, 2021
• Est. completion date: October 1, 2023

Study information

• Verified date: January 2022
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: Linna Wang, MD
• Phone: +86 13581990612
• Email: linna.wang[@]hengrui.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: October 1, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Biological:
• SHR-1701
Intravenous (IV) on Day 1 of each cycle

Drug:
• Famitinib
Famitinib, po, qd

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	First Affiliated Hospital of Gannan Medical University	Gannan	Jiangxi
China	The 1st Affiliated Hospital of Zhejiang Medical University	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The 2nd Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Jinan Central Hospital	Jinan	Shandong
China	General Hospital of Eastern Theater Command	Nanjing	Jiangsu
China	Qingdao Central Hospital	Qingdao	Shandong
China	Huashan Hospital,Fudan University	Shanghai	Shanghai
China	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	The 2nd Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RP2D	Recommended phase-2 dosage	First cycle (21 days)
Primary	Objective response rate (ORR)	Defined as complete or partial response per RECIST 1.1	up to approximately 3 years (anticipated)
Secondary	Clinically Significant Toxicity	Number of subjects in Phase I of combinational therapy part who experienced clinically significant toxicity	First cycle (21 days)
Secondary	AEs+SAEs	The incidence and severity of Adverse Events and Serious Adverse Events	up to approximately 3 years (anticipated)
Secondary	DCR	Disease Control Rate per RECIST 1.1	up to approximately 3 years (anticipated)
Secondary	DoR	Duration of Response per RECIST 1.1	up to approximately 3 years (anticipated)
Secondary	PFS	Progression-Free-Survival	up to approximately 3 years (anticipated)
Secondary	OS	OS is the time interval from the start of treatment to death from any cause or lost of follow-up	up to approximately 3 years (anticipated)
Secondary	6-month OS rate	6-month-overall survival rate	From the start of treatment to 6 months
Secondary	12-month-OS rate	12-month- overall survival rate	From the start of treatment to 12 months
Secondary	Cmax of SHR-1701	Maximum Plasma Concentration of SHR-1701	up to approximately 3 years (anticipated)
Secondary	C6h of Famitinib	Plasma Concentration of 6 hours after famitinb administration	up to approximately 6 months (anticipated)
Secondary	Cmax,ss		up to approximately 3 years (anticipated)
Secondary	AUC0-24h,ss		up to approximately 3 years (anticipated)]