Clinical trial NCT04588324: Study of SHR2150 (TLR7 Agonist) in Combination With Chemotherapy Plus PD-1 or CD47 Antibody in Subjects With Unresectable/ Metastatic Solid Tumors
Official title: Phase I/II Study Evaluating Safety and Clinical Efficacy of SHR2150 (TLR7 Agonist) in Combination With Chemotherapy Plus PD-1 or CD47 Antibody in Subjects With Unresectable/ Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: unresectable
metastatic
TLR7 agonist
anti-PD-1 antibody
anti-CD47 antibody
chemotherapy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of the combined regimen of SHR2150, chemotherapy, PD-1 or CD47 antibody
timeFrame: 60 days after last dose
measure: Identify a RP2D of SHR2150 when given in combined regimen
timeFrame: 30 days
measure: Object response rate (ORR)
timeFrame: 24 month
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: 24 months
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
measure: Time to Response (TTR)
timeFrame: 6 months
Other outcomes:
measure: Number of participants with laboratory test abnormalities
timeFrame: Approximately 6 months
measure: Number of participants with pathological immunology marker change
timeFrame: Approximately 6 months
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Biotherapeutic Department of Chinese PLA General Hospital
name: Weidong Han
role: PRINCIPAL_INVESTIGATOR
References: