A Phase Ⅰ/Ⅰb Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of Toripalimab (Anti-PD-1 Antibody) in Combination With Senaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors

Shanghai Junshi Bioscience Co., Ltd.0 sitesMarch 29, 2022

ConditionsAdvanced Cancer

InterventionsJS001+IMP4297

DrugsJS001+IMP4297

Overview

Phase: Phase 1
Intervention: JS001+IMP4297
Conditions: Advanced Cancer
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Primary Endpoint: DLT、AE、SAE、irAE
Status: Withdrawn
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a Phase I/Ib open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity and antitumor activity of toripalimab in combination with senaparib in patients with advanced solid tumors. The study consists of 2 parts, the Phase I part of the study will be a dose-escalation evaluation to determine the RP2D of senaparib to be administered in combination with the fixed dose of toripalimab, and the Phase Ib portion will further evaluate the RP2D and evaluate the efficacy of combination in specific types of advanced solid tumors.

Registry

clinicaltrials.gov

Start Date

March 29, 2022

End Date

June 6, 2024

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Junshi Bioscience Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Able to provide written informed consent and can understand and comply with the requirements of the study；
•Male or female patients, age ≥ 18 years;
•Patients with histologically or cytologically confirmed advanced (metastatic and/or unresectable) solid tumors that is incurable and have progressed during or after standard therapy or for which treatment is not available, or not tolerated;
•Patients are able to provide fresh or archival tumor tissues (FFPE block or unstained slides). In the absence of archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is recommended;
•Patient must have at least one measurable lesion as defined per RECIST v1.1;
•Eastern Cooperative Oncology Group (ECOG) Performalesce Status ≤1;
•Life expectancy ≥12 weeks;
•Vital organ function, defined as:
•Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 100 g/L.（Patients must not have required a blood transfusion or growth factor support ≤14 days before sample collection）； Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or calculated creatinine clearance ≥ 51 mL/min using Cockcroft-Gault equation for patients with creatinine levels \> 1.5×ULN； Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN, unless liver metastases are present, in which case they must be ≤ 5× ULN,ALP≤2.5 TIMES ULN (≤5 times ULN if tumor bone metastasis is present); Total bilirubin (TBIL) ≤ 1.5ULN; Patients with Gilbert syndrome should communicate with the sponsor medical examiner whether they can be enrolled in the group; Serum albumin ≥ 30 g/L； International standardized ratio (INR) or prothrombin time (PT) ≤ 1.5X ULN and activated partial thrombin time (aPTT) ≤ 1.5x ULN in patients who did not receive anticoagulant therapy; For those receiving anticoagulant therapy (e.g., low molecular weight heparin or warfarin), the anticoagulant dose should be stable for at least 4 weeks without dose adjustment; TSH within the normal range (if TSH is not within the normal range, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal range.); Urinary protein -/+, if urinary protein ≥2+, additional 24-hour urine protein quantification test is required, such as 24-hour urine protein quantification \<1g can be included in the group; Serum lipase or amylase ≤1.5 × ULN or \>1.5 × ULN(no clinical or imaging confirmed pancreatitis); Fridericia's QT interval (QTc) prolongation: female≤ 470 ms, male≤ 450 ms at screening.
•Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation;

Exclusion Criteria

•Major surgery (as defined by the investigator) within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery; Note: Local palliative treatment (eg. local surgery or radiotherapy) for isolated lesions is allowed, if not affecting the efficacy evaluation;
•Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 4 weeks; Note: Patients with previously treated brain metastases may participate provided they are stable and have no symptoms.Asymptomatic patients with brain metastases found at screening phase are eligible.Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
•Patient has an active autoimmune disease or autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
•Note: ① Autoimmune diseases include but are not limited to systemic lupus erythematosus, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism or multiple sclerosis; ② patients with vitiligo or in childhood asthma has complete remission, adult patients without any intervention can be incorporated into; ③ in chronic obstructive pulmonary disease (COPD), asthma need continuous use of bronchiectasis, inhaled corticosteroids, or local injection of corticosteroids can into the group of patients.
•Prior malignancy within the previous 5 years except for locally curable cancers that have apparently been cured (eg, basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast);
•Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease. Specific examples include, but are not limited to, uncontrolled hypertension (systolic blood pressure \>160 mmHg, diastolic blood pressure \>100 mmHg); recent (within 90 days) NYHA≥3 heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism; LVEF\<50%;; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent);
•Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drugs; Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year prior to screening;
•Patients who have a history of or are currently developingpneumonitisrequiring steroid treatment, including but not limited to interstitial pneumonia, radiation pneumonia, pulmonary fibrosis, or machine-induced pneumonia;
•Prior bone marrow allogeneic transplantation or solid organ transplantation;
•Patient has any known history of MDS/AML or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/AML;

Arms & Interventions

JS001+IMP4297

Intervention: JS001+IMP4297

Outcomes

Primary Outcomes

DLT、AE、SAE、irAE

Time Frame: 3 years

Safety endpoints: incidence and severity of DLT, adverse events (AE), serious adverse events (SAE), and immune-related adverse events (irAE); Abnormal changes in laboratory and other tests with clinical significance

MTD

Time Frame: 1 year

Maximum tolerated dose (MTD)

RP2D

Time Frame: 1 year

Recommended dose for phase II trial

ORR

Time Frame: 2 years

Efficacy endpoints: Objective response rate (ORR) per RECIST v1.1