Study of SHR2150 (TLR7 Agonist) in Combination With Chemotherapy Plus PD-1 or CD47 Antibody in Subjects With Unresectable/ Metastatic Solid Tumors

NCT ID: NCT04588324

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-10
• Study Completion Date: 2022-11-30

Brief Summary

This phase I/II trial aims to evaluate safety and efficacy of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. Patients will receive the combined regimen in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, three oral doses of SHR2150 will be combined with intravenous administration of chemotherapy and PD-1 or CD47 antibody. In the Phase 2 dose expansion portion, patients will be treated with the Recommended Phase 2 Dose (RP2D) of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody.

Detailed Description

Identification of T cell inhibitory signals, including PD-1/L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the cancer-immunity cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. SHR2150 is a small molecule agonist of toll-like receptors (TLRs) 7 designed to activate antigen-presenting cells and functions as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I/II, dose escalation/expansion study of a combined regimen of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. This study is designed to assess the safety, tolerability, RP2D and clinical efficacy of this regimen.

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose-Escalation

With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached.

Group Type: EXPERIMENTAL

SHR2150

Intervention Type: DRUG

Patients will receive escalating doses of SHR-2150 (starting dose 2 mg) in 3-week treatment cycles.

Anti-Cancer Agent

Intervention Type: DRUG

The previously resistant first-line cytotoxic regimens, anti-PD-1 antibody and/or anti-CD47 antibody will be administered intravenously Q3W.

Phase 2 Dose-Expansion

SHR2150 RP2D will be combined with chemotherapy plus PD-1 or CD47 antibody in 3-week treatment cycles.

Group Type: EXPERIMENTAL

Anti-Cancer Agent

Intervention Type: DRUG

The previously resistant first-line cytotoxic regimens, anti-PD-1 antibody and/or anti-CD47 antibody will be administered intravenously Q3W.

SHR2150

Intervention Type: DRUG

Patients will receive SHR-2150 at RP2D in 3-week treatment cycles.

Interventions

SHR2150

Patients will receive escalating doses of SHR-2150 (starting dose 2 mg) in 3-week treatment cycles.

Intervention Type: DRUG

Anti-Cancer Agent

The previously resistant first-line cytotoxic regimens, anti-PD-1 antibody and/or anti-CD47 antibody will be administered intravenously Q3W.

Intervention Type: DRUG

SHR2150

Patients will receive SHR-2150 at RP2D in 3-week treatment cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subjects must have histologically proven unresectable/ metastatic solid tumors.

2. ≥ 18 years old.

3. Life expectancy of at least 6 months.

4. Eastern Cooperative Oncology Group performance status 0-3.

5. Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.

6. Subjects must have received at least two frontlines therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.

7. Subjects must be off prior therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.

8. Adequate organ function.

9. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

10. Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.

2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.

3. Prior organ allograft.

4. Women who are pregnant or breastfeeding.

5. Women with a positive pregnancy test on enrollment or prior to investigational product administration.

6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han weidong

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weidong Han

Role: PRINCIPAL_INVESTIGATOR

Biotherapeutic Department of Chinese PLA General Hospital

Locations

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Weidong Han, M.D.

Role: CONTACT

hanwdrsw@sina.com

+861066937463

Facility Contacts

Weidong D Han, M.D.

Role: primary

hanwdrsw@sina.com

+86-10-66937463

C

Role: backup

Other Identifiers

CHN-PLAGH-BT-059

Identifier Type: -

Identifier Source: org_study_id