Anlotinib Plus Penpulimab for the Treatment of Sensitive Relapsed Small-Cell Lung Cancer

Study Overview
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Brief Summary
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Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development. It can inhibit the angiogenesis related kinase, such as VEGFR, FGFR, PDGFR, and tumor cell proliferation related kinase -c-Kit kinase. In the phase II ALTER1202 trial, patients who failed at least two kinds of systemic chemotherapy regimens (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 4.1 months and 7.3 months, the placebo group PFS and OS were 0.7 months and 4.9 months. Therefore, the combination of Anlotinib and Penpulimab (a new PD-1 inhibitor) is attempted for the treatment of sensitive relapsed small-cell lung cancer patients who were failure in the first-line treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS or OS.

Detailed Description
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This is a multicenter, single-arm, explorative clinical trial conducted in China to investigate the effectiveness and safety of Anlotinib Plus Penpulimab in patients of sensitive relapsed small-cell lung cancer. Eligible patients will receive Anlotinib plus Penpulimab: Anlotinib: 10mg orally daily on day 1 to 14 of a 21-day cycle. Penpulimab: 200mg by intravenous drip on day 1 of a 21-day cycle.

Official Title
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Anlotinib Plus Penpulimab for the Treatment of Sensitive Relapsed Small-Cell Lung Cancer: a Multicenter, Single-arm, Explorative Trial

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Anlotinib Plus Penpulimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed and dated informed consent Small cell lung cancer pathologically confirmed, with measurable nidus (RECIST 1.1) have failed for first-line chemotherapy have a time interval ≥ 3 months between relapse and the end of the last systemic chemotherapy ECOG PS: 0-1, Expected Survival Time: Over 3 months main organs function is normal the woman patients of childbearing age who must agree to take contraceptive methods (e.g. intrauterine device, contraceptive pill or condom) during the research and within another 8 weeks after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after it. Exclusion Criteria: have used Anlotinib or other antiangiogenic drugs before have used Penpulimab or other anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, as well as any other antibodies or drugs targeting T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (such as CD40, CD137, GITR, OX40, etc.) have failed for two times or beyond of platinum two drugs chemotherapy (except adjunctive chemotherapy, after which disease relapse or progression within 6 months，has been regarded as first-line therapy.) iconography (CT or MRI) shows obvious lung empty or necrotic tumor patients with brain or central nervous system metastases, including leptomeningeal disease, or CT/MRI examination revealed brain or leptomeningeal disease） (28 days before the random treatment has been completed and the symptoms of patients with brain metastases from stable can into the group, but need to the cerebral MRI, CT or vein angiography confirmed as without symptoms of cerebral hemorrhage) patients are participating in other clinical studies (other than non-interventional studies) less than 4 weeks from the end of the previous clinical study patients who had received chemotherapy, radiation, or other experimental anticancer therapy (except diphosphonate) within 4 weeks prior to the first dose of this study. Those who had previously received local radiotherapy were eligible if they met the following criteria: the end of radiotherapy was more than 4 weeks from the start of this study (brain radiotherapy was more than 2 weeks); In addition, the target lesions selected in this study were not in the radiotherapy area, or if the target lesion is within the radiotherapy area but progression has been confirmed other kinds of malignancies within 5 years or for now patients who have an active, known or suspected autoimmune disease, including a history of allogeneic organ transplantation, allogeneic hematopoietic stem cell transplantation, a history of being HIV positive, or a history of acquired immunodeficiency syndrome (AIDS) active or previously recorded inflammatory bowel disease (such as Crohn's disease, ulcerative colitis) have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT ULN > 1.5), with bleeding tendency or be treated with thrombolysis and anticoagulation have clinical significant hemoptysis occurred within 3 months before enrollment (daily hemoptysis more than half tablespoonl; Or clinical significant bleeding symptoms or bleeding tendency in the 4 weeks prior to grouping, such as gastrointestinal bleeding, hemorrhagic gastric ulcer (including gastrointestinal perforation and/or fistula, but gastrointestinal perforation or fistula has been surgically removed, admission is allowed), baseline fecal occulted blood ++ or above, unhealed wounds, ulcers or fractures, etc urine routines show urine protein≥ ++, or urine protein quantity≥ 1.0 g during 24 hours uncontrollable hypertensive (SBP≥ 160 mmHg, DBP≥100 mmHg, despite the best drug treatment) patients with severe cardiovascular disease: grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; According to NYHA standard, grade III to IV cardiac insufficiency, or echocardiography indicates left ventricular ejection fraction (LVEF) < 50%; patients with NCI-CTCAE grade II or greater peripheral neuropathy, except due to trauma Interstitial lung disease, uncontrolled medium to large serosal effusion (including pleural effusion, ascites, and pericardial effusion) after pumping treatment, aggravated chronic obstructive pulmonary disease, active pulmonary infection and/or acute bacterial or fungal respiratory disease requiring intravenous antibiotic treatment within 28 days have an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc have venous thromboembolism events within 6 months before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc have received live or attenuated vaccine within 30 days prior to the initial administration of Penpulimab, or was scheduled to receive live or attenuated vaccine during the study patients who have known a history of severe hypersensitivity to other monoclonal antibodies patients who have known a history of psychotropic substance abuse, alcohol abuse, or drug abuse uncontrolled active hepatitis after treatment (Hepatitis B: HBsAg positive and HBV DNA more than 1 x 10^4 copy /ml; Hepatitis C: HCV RNA is positive and liver function is abnormal); Combined with hepatitis b and hepatitis c infection serious diseases that endanger patients' safety or affect patients' completion of research, according to the researchers' judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib Plus Penpulimab<br>Anlotinib (10mg qd po d1-14, 21 days per cycle) and Penpulimab (200mg ivgtt d1) | Drug: Anlotinib Plus Penpulimab<br>* Anlotinib: 10mg orally daily on day 1 to 14 of a 21-day cycle. Penpulimab: 200mg by intravenous drip on day 1 of a 21-day cycle.<br>* Other names: Anlotinib & Penpulimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective Response Rate | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progress free survival | each 42 days up to PD or death (up to 24 months) | 
| OS | Overall Survival | From randomization until death (up to 24 months) | 
| DCR | Disease Control Rate | each 42 days up to intolerance the toxicity or PD or death (up to 24 months) | 
| Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability） | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Until 21 day safety follow-up visit |