Sintilimab With Pemigatinib in Patients With PD-L1-positive and FGFR Mutated Advanced Non-small Cell Lung Cancer

NCT05004974 | Recruiting Phase 2

• 1 other identifier: K2021085
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Lung cancer is the leading cause of death from cancer in China. In recent years, immune checkpoint inhibitor has gradually become a research hotspot, and it has continuously achieved huge breakthroughs. The FDA and NMPA have approved multiple PD-1/PD-L1 inhibitors for first-line or second-line treatment of advanced or metastatic NSCLC. But In clinical practice, there is still some controversy about PD-1 inhibitor monotherapy, especially for patients with low PD-L1 expression, the efficacy of monotherapy needs to be further improved. Strong genetic and functional evidence indicates that FGFR dysregulation can lead to the development and progression of cancer. Genetic alterations of FGFR1, FGFR2 and FGFR3 have been found in a variety of tumors. Squamous non-small cell lung cancer has about 13% of FGFR variants, while there are only 4% of any FGFR variants in lung adenocarcinoma. Studies of FGFR inhibitors in NSCLC show that AZD4575 has shown partial efficacy in FGFR partially mutated and expanded lung squamous cell carcinoma. FGFR pathway is involved in the regulation of the tumor immune microenvironment. In the tumor suppressor model of rectal cancer, it has been observed that FGFR2 overexpression promotes the expression of PD-L1 by activating JAK/STAT3 pathway, leading to tumor growth. In a lung cancer suppressor mouse model, the combination of FGFR inhibitor and PD-1 inhibitor can improve tumor remission and prolong survival. Based on the preliminary clinical data, this study assumes that Sintilimab(anti-PD-1) combined with Pemigatinib(FGFR inhibitor) can further improve efficay of advanced NSCLC with PD-L1 positive and FGFR1-3 mutation) including but not limited to FGFR amplification, rearrangement/fusion, mutation, etc.).

Conditions

Advanced Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The proportion of subjects who achieved complete remission (CR) or partial remission (PR) according to the RECIST1.1.

  6 weeks

Secondary Outcomes (5)

• Progression-free survival

  9 months

• Duration of remission

  6 months

• Time to remission

  6 weeks

• Disease control rate

  6 weeks

• Overall survival

  4 years

Study Arms (1)

Sintilimab with Pemigatinib

EXPERIMENTAL

Sintilimab combined with Pemigatinib every 3 weeks (Q3W): Sintilimab is administered every 3 weeks (200mg, IV), Pemigatinib 13.5 mg once daily (QD) orally, continuous administration.

Drug: Sintilimab; Drug: Pemigatinib

Interventions

Sintilimab DRUG

Sintilimab is administered every 3 weeks (200mg, IV).

Sintilimab with Pemigatinib

Pemigatinib DRUG

Pemigatinib 13.5 mg once daily (QD) orally, continuous administration.

Sintilimab with Pemigatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Patients confirmed by histology or cytology non-small cell lung cancer with stage IIIB-IIIC and stage IV (UICC and AJCC, 8th edition TNM staging) which is unresectable or unsuitable for radical concurrent radiochemotherapy;
• Not applicable to EGFR/ALK/ROS1 targeted therapy;
• Histologically confirmed PD-L1 positive (TPS≥1%);
• Histology confirmed FGFR1-3 mutations, including but not limited to amplification, mutation, fusion/rearrangement, etc.;
• According to RECIST v1.1 version, there is at least one measurable lesion.
• Not received any systemic anti-tumor therapy for advanced/metastatic diseases. For participants who have received adjuvant/neoadjuvant therapy, or have received radical radiochemotherapy for locally advanced disease, if the interval between disease progression or recurrence and the end of the last treatment is more than 6 months, these participants are allowed to be included in this study;
• Not used small molecule multi-target inhibitors (including Anlotinib, Lenvatinib, Sorafenib, etc.) that target the FGFR pathway;
• Have not previously received the following immune checkpoint inhibitor therapy: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or targeting another stimulating or synergistic inhibition of T cell receptors (including but not limited to CTLA-4 , OX-40, CD137, etc.);
• ECOG physical status is 0-1;
• Expected survival time\> 3 months;
• The participants are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy must be completed at least 2 weeks before the first study drug is administered (the end of palliative radiotherapy for the central nervous system should be 4 weeks before the first study drug administration), and the radiotherapy-related toxicity is restored to less than or equal to 1 degree (CTCAE 5.0, except for hair loss), no corticosteroid treatment is required, and radiation pneumonia is confirmed to be excluded;
• Sufficient organ function, participants need to meet the following laboratory indicators:
• The absolute value of neutrophils (ANC) ≥1.5x10\^9/L when no granulocyte colony stimulating factor is used in the past 14 days;
• Platelets ≥100×10\^9/L in the case of no blood transfusion in the past 14 days, ;

You may not qualify if:

• Diagnosis of other malignant diseases other than non-small cell lung cancer within 5 years before the first administration (excluding radically cured skin basal cell carcinoma, skin squamous epithelial carcinoma and/or radically excised carcinoma in situ);
• Currently participating in interventional clinical research treatment, or received other research drugs or used research devices within 4 weeks before the first administration;
• Received anti-tumor drug treatment (including Chinese herbal medicine with anti-tumor indications) within 28 days before using the first administration;
• Before starting treatment, have not fully recovered from toxicity and/or complications caused by any intervention (ie, ≤ Grade 1 or reached baseline, excluding fatigue or hair loss) ;
• Meningeal metastasis/cancerous meningitis or central nervous system metastasis with known symptoms. For asymptomatic participants or participants with stable brain metastases after local treatment, those participants are also allowed to join the group if the following conditions are met :1) There are measurable lesions outside the central nervous system; 2) No symptoms of the central nervous system or no aggravation of symptoms within at least 2 weeks; 3) There is no evidence of imaging progress at least 4 weeks before the first administration; 4) Those who do not need glucocorticoid therapy or stop glucocorticoid therapy within 14 days before the first study drug administration;
• There is clinically uncontrollable pleural effusion/abdominal effusion (patients who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included);
• Known human immunodeficiency virus (HIV) infection history or confirmed positive immunological test results;
• Acute or chronic active hepatitis B (defined as HBsAg positive and the HBV-DNA copy number is greater than the upper limit of the normal value of the laboratory department of the research center), active hepatitis C (HCV) infection (defined as HCV antibody positive and Patients whose HCV-RNA level is higher than the lower limit of detection), or patients with both hepatitis B surface antigen (HbsAg) and anti-HCV antibody positive at the same time. Note: Hepatitis B participant who meet the following criteria can also be included in the group:1) Before the first administration, the HBV viral load is less than 1000 copies/ml (200 IU/ml), and the participant should receive anti-HBV treatment during the entire study drug treatment period to avoid viral reactivation 2) For participants with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is no need to receive preventive anti-HBV treatment, but close monitoring of virus reactivation is required.
• There are any serious or uncontrollable systemic diseases, including:1) Clinically significant or uncontrolled heart diseases, including: uncontrolled arrhythmia (pacemaker is allowed or those with atrial fibrillation and well-controlled heart rate); resting electrocardiogram indicated major abnormalities with severe symptoms that are difficult to control in rhythm, conduction or morphology , such as complete left bundle branch block, heart block above Ⅱ degree, ventricular arrhythmia or atrial fibrillation; unstable angina, acute myocardial infarction, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) grade ≥ 2 within 6 months before the first administration; 2) There are ECG changes or medical history that the investigator considers to be clinically significant; QTcF interval\> 480 ms, for participants with indoor conduction block (QRS interval\> 120 ms), JTc interval can be used instead of QTc interval (If JTc is used instead of QTc, JTc must be ≤340 ms); 3) Uncontrollable hypertension, systolic blood pressure\> 160 mmHg or diastolic blood pressure\> 100 mmHg after the best medical treatment, history of hypertensive crisis or hypertensive encephalopathy; 4) There is a serious infection in the active phase or poor clinical control; 5) There is clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction; 6) Liver diseases such as decompensated liver disease, hepatic encephalopathy, hepatorenal syndrome or Child-Pugh Class B and more severe liver cirrhosis, acute or chronic active hepatitis; 7) Poor control of diabetes (fasting blood glucose (FBG)\> 10mmol/L); 8) Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantitation is confirmed to be greater than 1.0 g;
• Have received a major surgical operation (except for surgery for the purpose of biopsy) within 4 weeks before the first administration or are expected to undergo major surgery during the study treatment;
• Have received systemic systemic treatment with anti-lung cancer Chinese patent medicines or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural fluid) within 2 weeks before the first administration;
• An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
• Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhaled or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first administration of the study; Note: The use of physiological doses of glucocorticoids (≤10 mg/day prednisone or equivalent drugs) is allowed;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• A history of non-infectious pneumonia requiring glucocorticoid therapy within 1 year before the first administration, or current clinically active interstitial lung disease;

Sponsors & Collaborators

• The Fourth Affiliated Hospital of Zhejiang University School of Medicine: lead
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator

Study Sites (1)

The Fourth Affiliated Hospital of Zhejiang University

Yiwu, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Interventions

sintilimab; pemigatinib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: August 13, 2021
• Study Start: April 26, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)