A Single Arm，Open Label，Multi-centers，Phase 2 Study, Aimed to Evaluate the Efficacy and Safety of Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection (609A) Combined With Doxorubicin Hydrochloride in the Treatment of Metastatic/Unresectable Non-specific Soft Tissue Sarcoma
Overview
- Phase
- Phase 2
- Intervention
- 609A
- Conditions
- Sarcoma, Soft Tissue
- Sponsor
- Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Recommended phase II dose (RP2D) (Part 1)
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a single arm, open label, phase 2 study aimed to evaluate the efficacy and safety of the combination recombinant anti-PD-1 humanized monoclonal antibody injection (609A) and doxorubicin hydrochloride in the treatment of metastatic/unresectable non-specific soft tissue sarcoma
Detailed Description
This is a single-arm, open, multi-center phase 2 study aimed at evaluating the efficacy and safety of 609A combined with doxorubicin hydrochloride in patients with metastatic/unresectable non-specified soft tissue sarcoma. This study is divided into the first part (safety introduction period) and the second part (phase II). Part 1: Security lead-in period The safety lead-in period adopts a single-arm, open design to evaluate the safety, tolerability and preliminary effectiveness of 609A combined with doxorubicin hydrochloride. Which aimed to explore the Recommended phase II dose (RP2D). Part 2: Phase 2 This part adopts a single-arm, open, Simon two-stage design to further evaluate the anti-tumor efficacy and safety of 609A combined with doxorubicin hydrochloride.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand and voluntarily sign an informed consent form;
- •Age ≥ 18 years old when signing the informed consent form, regardless of gender;
- •Agree to provide biopsy tissue samples or archived tumor tissue samples (part 1 is voluntary);
- •Unresectable (including patients who refuse surgical resection) or metastatic unspecified soft tissue sarcoma confirmed by histology/cytology (subtypes allowed to be included include: synovial sarcoma, mucinous/round cell liposarcoma , Uterine leiomyosarcoma, pleomorphic liposarcoma, myxofibrosarcoma, epithelioid sarcoma, pleomorphic rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, scalp and facial angiosarcoma, dedifferentiated liposarcoma) patients ；
- •Patients who have not received systemic drug therapy in the past;
- •According to the RECIST V1.1 solid tumor efficacy evaluation standard, the patient has at least one imaging measurable lesion;
- •ECOG score 0 or 1;
- •Expected lifetime ≥ 3 months;
- •The organ function level must meet the following requirements:
- •The absolute value of neutrophils (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥100×109/L; hemoglobin (Hb) ≥90 g/L or ≥5.6 mmol/L (not accepted within 14 days) Blood transfusion, albumin or use of EPO, G-CSF);
Exclusion Criteria
- •Received radiotherapy covering more than 30% of the bone marrow area or carried out large-area irradiation within 4 weeks before the first administration (palliative radiotherapy for bone or palliative radiotherapy for superficial lesions is allowed, and it has ended 14 days before the first administration );
- •Received Chinese medicine or Chinese medicine preparation with anti-tumor as indication within 2 weeks or 5 half-life period (whichever is the elder) before the first administration;
- •Those who have participated in and received clinical trials of investigational drugs or interventional devices 4 weeks before the first administration or at least 5 half-lives of the drug (whichever is the elder);
- •Vaccination with live attenuated vaccine within 4 weeks before the first administration (seasonal influenza vaccine for injection is generally an inactivated vaccine, which is allowed to be used; while intranasal influenza vaccine \[such as flu spray\] is a live attenuated vaccine, which is not Allowed)
- •Use moderate or strong CYP3A4, P-glycoprotein, CYP2D6 inhibitors and CYP3A4, P-glycoprotein inducers within 1 week before the first administration;
- •Any toxicity related to previous radiotherapy has not recovered to ≤ Grade 1 (except for hair loss or treatment-related Grade 2 peripheral neuropathy);
- •Patients with active central nervous system (CNS) metastasis and/or cancerous meningitis found in a known or screening phase examination;
- •Spinal cord compression that has not been cured by surgery and/or radiotherapy;
- •Accompanied by unstable pleural effusion or ascites or pericardial effusion with obvious symptoms (those with stable clinical symptoms after treatment with pleural effusion or ascites or pericardial effusion can be included in the group);
- •Those who have a history of other malignant tumors, except for malignant tumors that have undergone radical resection and have not recurred within 5 years after surgery, such as cervical carcinoma in situ and skin basal cell carcinoma;
Arms & Interventions
experimental group
609A combined with doxorubicin hydrochloride
Intervention: 609A
experimental group
609A combined with doxorubicin hydrochloride
Intervention: doxorubicin hydrochloride
Outcomes
Primary Outcomes
Recommended phase II dose (RP2D) (Part 1)
Time Frame: At the end of Cycle 2 (each cycle is 21 days)
RP2D of the combination 609A and doxorubicin hydrochloride.
Adverse events (Part 1)
Time Frame: up to 2 years.
Evaluate the safety of the combinations According to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) .
Objective Response Rate (ORR) (part 2)
Time Frame: Up to 2 years .
Evaluated per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT. Complete Response (CR) is a complete elimination of the tumor; Partial Response (PR) is 30% reduction. If a subject experienced a PR, this was required to be confirmed with a second scan at the next appropriate cycle.
Secondary Outcomes
- Maximum Plasma Concentration (Cmax) (Part 2)(Up to 2 years.)
- Overall Survival (OS) (Part 1+2)(Up to 2 years .)
- incidence of anti-609A antibodies(Part 1+2)(Up to 2 years.)
- Objective Response Rate (ORR) (part 1)(Up to 2 years.)
- Median Progression-free Survival (PFS) (Part 1+2)(Up to 2 years .)
- Duration of Response(Part 1+2)(Up to 2 years.)
- Adverse events (Part 2)(Up to 2 years.)
- Area Under the Curve (AUC) (Part 2)(Up to 2 years.)