Trial Title:
Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients
NCT ID:
NCT05751187
Condition:
Non-squamous NSCLC
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Folic Acid
Vitamin B 12
Dexamethasone
Bevacizumab
Pembrolizumab
Carboplatin
Pemetrexed
Conditions: Keywords:
EGFR exon 20 insertion
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Pembrolizumab was given as 200 milligrams (mg) via intravenous (IV) infusion over 30
minutes on Day 1 of each 21-day cycle.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Biological
Intervention name:
Bevacizumab
Description:
Bevacizumab was given as 15 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day
cycle.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed was given as 500 mg/m^2 via intravenous (IV) infusion (with vitamin
supplementation) on Day 1 of each 21-day cycle for 4-6 cycles.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin was given as 75 mg/m^2 via intravenous (IV) infusion (administered
approximately 30 minutes after pemetrexed infusion) on Day 1 of each 21-day cycle for 4-6
cycles.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin was given as Aare Under the Curve (AUC) 5 (5 mg/mL/min; over 15-60 min) via
intravenous (IV) infusion (administered immediately after pemetrexed infusion) on Day 1
of each 21-day cycle for 4-6 cycles.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Dietary Supplement
Intervention name:
Folic acid 350-1000 μg
Description:
Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the
first dose of pemetrexed, and folic acid dosing must continue during the full course of
therapy and for 21 days after the last dose of pemetrexed.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Dietary Supplement
Intervention name:
Vitamin B12 1000 μg
Description:
Intramuscular injection in the week preceding the first dose of pemetrexed and once every
3 cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as
pemetrexed administration.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Dexamethasone 4 mg
Description:
For prophylaxis; orally twice per day (or equivalent). Taken the day before, the day of,
and the day after pemetrexed administration.
Arm group label:
Pembrolizumab + Bevacizumab + Chemotherapy
Summary:
This study is designed to evaluate the efficacy and safety of Pembrolizumab in
combination with Bevacizumab and chemotherapy in advanced or metastatic non-squamous
non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients
with locally advanced (stage III B/III C), metastatic or recurrent (stage IV)
nonsquamous NSCLC confirmed by histology or cytology who are unable to undergo
surgery and radical concomitant radiochemotherapy and are confirmed to have at least
one measurable lesion according to RECIST 1.1.
2. Patients harboring exon 20 insertions detected by ARMS or NGS or other approved
methods.
3. Age ≥18 years and ≤75 years.
4. ECOG PS score: 0 to 1
5. Have a life expectancy of at least 3 months.
6. Have not received prior systemic treatment including chemotherapy, checkpoint
inhibitors, TKIs, and anti-angiogenesis agents for their advanced/metastatic NSCLC.
Subjects who received adjuvant or neoadjuvant therapy including immunotherapy are
eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior
to the development of advanced/metastatic disease. Palliative radiotherapy must be
completed 7 days before the first dose of study drugs and participants must have
recovered from all radiation-related toxicities, not require corticosteroids, and
not have had radiation pneumonitis.
7. Have adequate organ function as defined in the following： (1) Adequate bone marrow
function Absolute neutrophil count(ANC) ≥ 1500/uL; Platelets≥10x104/uL; Hemoglobin
≥9.0g/dL or ≥5.6 mmol/L; (2) Adequate kidney function Creatinine≤ 1.5 x upper normal
limit (ULN), OR Measured or calculated creatinine clearance (GFR can also be used in
place of creatinine or CrCl) ≥30 mL/min for the participant with creatinine levels
>1.5 × institutional ULN (3) Adequate liver function Total bilirubin ≤ 1.5 x upper
normal limit (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin
levels >1.5 × ULN; Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 xULN (≤ 5.0 x ULN
if hepatic metastases); Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0x
ULN if hepatic metastases); (4) Coagulation function International normalized ratio
(INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 ×
ULN unless the participant is receiving anticoagulant therapy as long as PT or aPTT
is within the therapeutic range of intended use of anticoagulants.
8. A male participant must agree to use contraception during the treatment period and
plus an additional 90 days (a spermatogenesis cycle) for study treatments after the
last dose of study treatment and refrain from donating sperm during this period; A
female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies: a. Not a woman
of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees
to follow the contraceptive guidance in Appendix 3 during the treatment period and
plus 30 days (a menstruation cycle) for study treatments after the last dose of
study treatment.
9. The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial.
10. Archival tumor tissue sample or newly obtained [core, incisional, or excisional]
biopsy of a tumor lesion not previously irradiated has been provided.
Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides.
Newly obtained biopsies are preferred to archived tissue.
11. For hepatitis B-positive subjects:
(1) Participants who are HBsAg positive are eligible if they have received HBV antiviral
therapy for at least 4 weeks and have an undetectable HBV viral load prior to enrollment.
(2) Participants should remain on anti-viral therapy throughout the study intervention
and follow local guidelines for HBV anti-viral therapy post-completion of the study
intervention.
(3) Participants with a history of HCV infection are eligible if HCV viral load is
undetectable at screening.
(4) Participants must have completed curative anti-viral therapy at least 4 weeks prior
to enrollment.
Exclusion Criteria:
1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer);
2. Patients who have received systemic treatment for advanced/metastatic disease
especially have 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, CTLA-4, OX 40, CD137);
3. Patients concurrently with 19del or 21L858R or other mutation types located in exon
18-21
4. Patients who are known to have active brain metastases diagnosed by CT or MRI at the
time of screening, however, participants with previously treated brain metastases
may participate provided they are radiologically stable, i.e. without evidence of
progression for at least 4 weeks by repeat imaging (note that the repeat imaging
should be performed during study screening), clinically stable and without the
requirement of steroid treatment for at least 14 days prior to the first dose of the
study intervention.;
5. Patients with severe and/or uncontrolled diseases, such as:
(1) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction
within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood
pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); (2)
Active or uncontrolled serious infection; (3) Liver diseases such as cirrhosis,
decompensated liver disease, acute or chronic active hepatitis; (4) Not completely
controlled eye inflammation or eye infection, or any condition that may lead to the
above-mentioned ocular diseases (5) Poorly controlled diabetes (fasting blood glucose
(FBG) > 10mmol/L); (6) Routine urine test result indicates that urine protein ≥++, and
24-hour urine protein quantitation is confirmed to be > 1.0 g; (7) Active tuberculosis,
etc.; (8) Uncontrolled hypercalcemia (> 1.5 mmol/L calcium ion or calcium > 12 mg/dL or
corrected serum calcium > ULN), or symptomatic hypercalcemia requiring continued
diphosphate therapy; (9) Long-term unhealed wounds or fractures; 6. Patients who have a
history of psychotropic drug abuse and cannot abstain from it or have mental disorders;
7. Patients who are known to have severe allergies (≥ grade 3) to active ingredients and
any excipients of pembrolizumab 8. Patients who have other malignant tumors (except
radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time;
patients who are evaluated by the investigator to have concomitant diseases that
seriously endanger the safety of the patients or affect the patients completing the
study.
9. The subjects or their sexual partners cannot or refuse to take effective
contraceptive measures during the clinical trial 10. Pregnant or breast-feeding
women 11. Patients in other situations who are evaluated by the investigator to be
ineligible to be enrolled; 12. Has received a live vaccine or live-attenuated
vaccine within 30 days before the first dose of the study intervention.
Administration of killed vaccines is allowed (such as COVID-19 vaccines).
13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of the study drug.
14. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with the 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 and is allowed.
15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
16. Has a known history of Human Immunodeficiency Virus (HIV) infection. 17. Has a
history or current evidence of any condition, therapy, laboratory abnormality, or
other circumstance that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, such that it is not
in the best interest of the participant to participate, in the opinion of the
treating investigator.
18. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
19. Has had an allogeneic tissue/solid organ transplant. 20. Is currently participating
and receiving study therapy or has participated in a study of an investigational
agent and received study therapy or used an investigational device within 4 weeks
prior to administration of pembrolizumab.
21. Patients who have contraindications of antiangiogenic therapy, including the
presence of cavities, and bleeding tendencies judged by the treating physician.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Chest Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Baohui Han, MD, PhD
Phone:
+86-18930858216
Email:
18930858216@163.com
Start date:
June 27, 2023
Completion date:
March 30, 2027
Lead sponsor:
Agency:
Shanghai Chest Hospital
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Shanghai Chest Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05751187
