ALTER-GO-020: A Phase II Study of Anlotinib Combined With Penpulimab in Subjects With Gynecological Cancer
Study Details
Study Description
Brief Summary
This is a single-arm, open-label, phase II clinical trial to evaluate the efficacy and safety of penpulimab combined with anlotinib in subjects with gynecological cancer, including 23 ovarian cancer，37 endometrial cancer，26 cervical cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Penpulimab+Anlotinib Penpulimab 200 mg IV on Day 1 of each 21-day cycle plus Anlotinib capsules 12mg given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) |
Drug: Penpulimab
Penpulimab is a humanized monoclonal antibody targeting programmed cell death-1 (PD-1), which prevents PD-1 from binding to PD-L1 and PD-L2 receptors on tumor cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.
Drug: Anlotinib
A multi-target receptor tyrosine kinase inhibitor
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) [up to 96 weeks]
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR)
Secondary Outcome Measures
- Progression free survival (PFS) [up to 96 weeks]
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
- Duration of Response (DOR) [up to 96 weeks]
Time from tumor first assessment to CR or PR to first assessment to PD (Progressive Disease) or death from any cause
- Disease control rate（DCR） [up to 96 weeks]
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).
- Overall Survival (OS) [up to 120 weeks]
OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Understood and signed an informed consent form;
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18 years and older, female, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, life expectancy ≥3 months;
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Patients suffering from one of the following tumors：
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Histologically confirmed platinum-resistant or -refractory epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer, and at least treated with one line of platinum-based chemotherapy;
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Newly diagnosed, histologically-confirmed with residual disease after surgery, or inoperable stage III-IV endometrial carcinoma, or recurrent endometrial cancer patients, and na?ve to first line systemic anti-cancer treatment for recurrent/metastatic disease (Prior adjuvant chemotherapy and/or neoadjuvant chemotherapy with platinum-based regimens, or concurrent chemoradiation is permitted);
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Histologically confirmed persistent, recurrent, or stage IVB squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy (except when concurrently administered with radiotherapy) and is not amenable to curative treatment (such as with surgery and/or radiation).
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At least one measurable lesion according to the RECIST 1.1;
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Demonstrates adequate organ function:
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Blood routine inspection: Hemoglobin (HB) >= 90 g/L; The absolute value of neutrophil (ANC) >= 1.5x109/L;Platelets (PLT) >= 100x109/L;
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Blood biochemical inspection: Serum creatinine (Cr) <= 1.5 ULN, or creatinine clearance (CCr) >= 60mL / min; Total bilirubin (TBIL) <= 1.5 ULN, or direct bilirubin <= 1.0 ULN; AST and ALT <= 2.5 ULN.
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Blood coagulation function: Activated partial thromboplastin time, international standardized ratio adn prothrombin time <=1.5 ULN;
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Cardiac Function: left ventricular ejection fraction (LVEF) >=50%;
- Women of child-bearing potential must agree to use contraceptive measures (such as intrauterine devices or condoms) during the study and for 6 months after the end of the study, and have a negative serum pregnancy test within 7 days of enrollment, and must be non lactating subjects.
Exclusion Criteria:
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Has other non-epithelial ovarian tumors or borderline ovarian epithelial tumors; has carcinosarcoma, endometrial leiomyosarcoma, endometrial stromal sarcoma, or other high-grade sarcoma; has small cell carcinoma of the cervix;
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Other malignant tumors that have appeared or are currently present within 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors;
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Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137);
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Has received prior therapy with tyrosine kinase inhibitors that target VEGFR, such as pazopanib, sorafenib, regorafenib, apatinib and other drugs; but previous bevacizumab treatment is allowed, provided that the treatment is stopped for more than 4 weeks before enrollment;
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Has received prior radiotherapy within 4 weeks prior to enrollment (participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis - a 2-week washout is permitted for palliative radiation to non-CNS disease and vaginal brachytherapy);
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Has received prior hormonal therapy for the treatment of endometrial carcinoma within 1 week before enrollment;
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Expect to use any active vaccine against infectious diseases (such as influenza vaccine, chickenpox vaccine, etc.) within 28 days before the first dose or during the study period;
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Patients diagnosed with immunodeficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose> 10mg / day prednisone or other effective hormones) and continue to use it within 2 weeks before the first dose;
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Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first dose;
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Subjects known to be allergic to the study drug or any of its excipients or have experienced a severe allergic reaction to other monoclonal antibodies;
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Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis;
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Has any bleeding or bleeding event ≥ CTC AE Grade 3 or unhealed wounds, ulcers or fractures within 4 weeks before enrollment;
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Has clinically significant thyroid dysfunction before enrollment;
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Has multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
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Has any severe acute complications before enrollment:
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Blood pressure control is not ideal (systolic pressure >= 150 mmHg, diastolic pressure >= 100 mmHg);
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Patients had Unstable angina pectoris, myocardial infarction, ≥grade 2 congestive heart failure, or arrhythmia requiring treatment (including QTc ≥480 ms) within 6 months before enrollment;
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Active or uncontrolled serious infection (≥CTC AE grade 2 infection);
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Epidemiological test results during the screening period showed that any of the following is met: * HBsAg positive and HBV DNA exceeds the upper limit of normal value (those who fall within the normal range after antiviral treatment can be included); * Anti-HCV positive and HCV RNA positive; * HIV positive;
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Poorly controlled diabetes (fasting blood glucose ≥ grade 2);
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Had an arterio / venous thrombotic / carcinothrombotic event within 6 months, such as cerebrovascular accident (including transient ischemic attack, intracerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism, and Hypertensive crisis or hypertensive encephalopathy;
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Exacerbated chronic obstructive pulmonary disease (COPD) or other respiratory diseases that require hospitalization, or have active lung infections and/or acute bacterial or fungal infections that require intravenous antibiotic treatment within 28 days before the first dose.
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Has participated in other anti-tumor intervention clinical trials within 4 weeks before the first medication;
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According to the judgement of the researchers, there are other factors that may lead to the termination of the study. For example, other serious diseases including mental disorders need to be treated together, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data and samples.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100730 |
| 2 | Sicchuan cancer hospital | Chengdu | Sichuan | China | 610000 |
Sponsors and Collaborators
- Sichuan Cancer Hospital and Research Institute
Investigators
- Principal Investigator: Guonan Zhang, Sichuan Cancer Hospital and Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALTERGO020