Clinical trial NCT06132217: A Study of Simmitinib Plus SG001 in Advanced Solid Tumors
Official title: A Phase I/II Study To Evaluate The Safety, Tolerability, Pharmacokinetic Profile And Preliminary Efficacy Of Simmitinib Plus SG001 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-11-15
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label Phase I/II trial of simmitinib plus SG001 in patients with advanced solid tumors. Phase I will determine and confirm the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) for simmitinib in combination with SG001 in patients with advanced solid tumors. Phase 2 (Expansion) will evaluate the safety and efficacy of the combination in 3 cohorts at the RP2D from Phase I.


Eligibility criteria: Inclusion Criteria:

1. Have fully understood and voluntarily sign the ICF for this study;
2. Age of 18-75 years (inclusive);
3. Dose escalation phase: patients with histologically or cytologically confirmed inoperable or metastatic advanced solid tumors;
4. Dose expansion phase: patients who have failed standard treatment (PD or intolerable toxicity after treatment), have no available standard treatment.According to the previous data, the specific tumor cohort was expanded.
5. In the expansion phase, patients should agree to provide tissue specimens for detection of PD-L1 expression levels and/or MSI or dMMR status;
6. At least one measurable lesion according to RECIST 1.1;
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1;
8. Adequate organ function, defined as:

Neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 100× 10\^9/L; Hemoglobin (Hb) ≥ 90 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases); Serum total bilirubin (TBIL) ≤ 1.5 × ULN; Serum creatinine ≤ 1.5 × ULN; Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio(INR)≤1.5 × ULN; Thyroid Stimulating Hormone (TSH)≤ULN; Left ventricular ejection fraction (LVEF)≥50%; Male and female patients of childbearing age must agree to take effective contraceptive measures during treatment and within 6 months after the last dose of treatment.

Exclusion Criteria:

1. Patients who have previously received any anti-tumor therapy within 4 weeks prior to the first dose;
2. Urine protein ≥ ++ and 24 h urine protein \> 1.0g at screening period;
3. Symptomatic central nervous system (CNS) metastases or meningeal metastases;
4. Patients who have previously received any live attenuated vaccine within 4 weeks before the first use of the study treatment or are expected to received any live attenuated vaccine during the study;
5. History of allergic reactions attributed to any monoclonal antibody, and uncontrolled history of allergic asthma;
6. Patients with other types of malignant tumors within 5 years prior to the screening, except for radically resected, non-recurrent skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical cancer in situ, or other carcinoma in situ;
7. Patients with any active autoimmune disease requiring systemic therapy within 2 years prior to the first dose;
8. Patients with bleeding tendency; active bleeding or a history of heavy bleeding within the past 6 months;
9. Presence of any severe and/or uncontrolled disease before starting treatment;
10. Any active infection requiring antibiotics or hormones systemic treatment by intravenous infusion within 14 days prior to the first dose;
11. Dose expansion phase: Prior systemic therapy with immunosuppressants or immunoagonists targeting PD-1, PD-L1, CTLA-4, etc;
12. Dose expansion phase: Prior systemic therapy with Antiangiogenic drugs including Anlotinib, Afatinib , Lenvatinib, Sorafenib and Fruquintinib, etc;

Primary outcomes:
measure: Dose Escalation Phase: Dose Limited Toxicity (DLT)
timeFrame: From Cycle 1 Day 1 to Cycle 1 Day 28(each cycle is 28 days)
measure: Dose Escalation Phase: Maximum Tolerated Dose (MTD)
timeFrame: From Cycle 1 Day 1 to Cycle 1 Day 28(each cycle is 28 days)
measure: Dose Escalation Phase: Recommended Phase 2 Dose (RP2D)
timeFrame: From Cycle 1 Day 1 to Cycle 1 Day 28(each cycle is 28 days)
measure: Dose Escalation Phase-Incidence rate of Adverse Event (AE).
timeFrame: From first dose to 30 days post the last dose, with approximately 3 years
measure: Dose Expansion Phase - Objective Response Rate (ORR) evaluated by Independent Review Committee (IRC) or investigators in advanced solid tumor based on RECIST 1.1.
timeFrame: Up to approximately 3 years.
Secondary outcomes:
measure: Plasma Concentration of simmitinib .
timeFrame: Up to approximately 3 years.
measure: Plasma Concentration of SG001
timeFrame: Up to approximately 3 years.
measure: Immunogenicity Assessments for Anti-drug Antibody
timeFrame: Up to approximately 3 years.
measure: Dose Escalation Phase: ORR
timeFrame: Up to approximately 3 years.
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years.
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 3 years.
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years.
measure: Duration of Objective Response (DOR)
timeFrame: Up to Approximately 3 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
References: