Pembrolizumab With Standard Cytotoxic Chemotherapy in Treatment Naive NSCLC Patients With Asymptomatic Brain Metastases

NCT04967417 | Completed Phase 2 Results

• 1 other identifier: 2021-06-008
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II single center, open-label, single arm study in patients with advanced non-small cell lung cancer (stage IV) with brain metastases. This study will be treated with combination of Pembrolizumab 200mg plus platinum doublet based on histology subtypes.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Intracranial Objective Response Rate

  Intracranial objective response is defined as the investigator's best non-confirmed response as CR (complete response) or PR (partial response) as determined using RECIST v1.1. Subjects who do not meet these criteria, including those without a post-baseline tumor assessment, are considered non-responders. Intracranial objective response rate (iORR) is defined as the proportion of subjects who achieved an objective response among all subjects treated with the IP who had measurable disease at baseline. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of t the diameters of target lesion.

  Up to 24 months

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  The time until the date of either disease progression or the all-cause mortality from the date of IP administration. Up to 30 months

• Overall Survival (OS)

  The time until defined by date of all-cause mortality from the date of IP Administration. Up to 30 months.

• Intracranial Duration of Response

  Up to 30 months.

• Intracranial Progression-free Survival

  Up to 30 months.

• Objective Response Rate

  Up to 30 months.

Other Outcomes (1)

• Exploratory Analyses Based on PD-L1 Expression

  Up to 30 months.

Study Arms (2)

Non-squamous cell carcinoma

EXPERIMENTAL

* 4 cycles of pemetrexed 500mg/m2 + carboplatin AUC 5.0 + pembrolizumab 200mg every 3 weeks * Followed by pemetrexed 500mg/m2 + pembrolizumab 200mg every 3 weeks up to 35 cycles

Drug: Pemetrexed, Carboplatin, Pembrolizumab

Squamous cell carcinoma

EXPERIMENTAL

* 4 cycles of paclitaxel 200mg/m2 + carboplatin AUC 6.0 + pembrolizumab 200mg every 3 weeks * Followed by pembrolizumab 200mg every 3 weeks up to 35 cycles

Drug: Paclitaxel, Carboplatin, Pembrolizumab

Interventions

Pemetrexed, Carboplatin, Pembrolizumab DRUG

* Pemetrexed 500mg/m2 * Carboplatin AUC 5.0 * Pembrolizumab 200mg

Also known as: Alimta, Preizer carboplatin, keytruda

Non-squamous cell carcinoma

Paclitaxel, Carboplatin, Pembrolizumab DRUG

* Paclitaxel 200mg/m2 * Caboplatin AUC 6.0 * Pembrolizumab 200mg

Also known as: Anzatax, Preizer carboplatin, keytruda

Squamous cell carcinoma

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 19 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage IV non-small cell lung cancer with brain metastases will be enrolled in this study.
• Must have at least one intracranial target lesion. Intracranial lesion must be equal or greater than the 10mm in longest diameter.
• Have confirmation that EGFR or ALK-directed therapy is not indicated
• Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Otherwise, previously treated with radiation is not considered as measurable lesion.
• Have not received prior systemic treatment for their advanced/metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
• Have a life expectancy of at least 3 months
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Have adequate organ function
• Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days 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 for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to IP administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 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 (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior to IP administration as a metastatic disease treatment, including tyrosine kinase inhibitor.
• Had major surgery \< 3 weeks prior to first dose
• No measurable CNS lesion other than CNS lesion treated with stereotactic radiotherapy or surgery
• Had received whole brain radiotherapy or stereotactic radiotherapy to CNS disease.
• Has received prior radiotherapy within 1 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• 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 study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, thyroid cancer or early gastric cancer or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. 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 and is allowed.
• Has a history of (non-infectious) pneumonitis that currently required steroids or has current pneumonitis.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Gangnamgu, 06351, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Carboplatin; pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Myung-Ju Ahn
• Organization: Samsung Medical Center

silkahn@skku.edu

+82-2-3410-3438

Study Officials

• Myung-Ju Ahn, MD, phD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Non-squamous cell carcinoma: 4 cycles of pemetrexed 500mg/m2 + carboplatin AUC 5.0 + pembrolizumab 200mg every 3 weeks Followed by pemetrexed 500mg/m2 + pembrolizumab 200mg every 3 weeks up to 35 cycles Squamous cell carcinoma: 4 cycles of paclitaxel 200mg/m2 + carboplatin AUC 6.0 + pembrolizumab 200mg every 3 weeks Followed by pembrolizumab 200mg every 3 weeks up to 35 cycles

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: July 19, 2021
• Study Start: May 26, 2022
• Primary Completion: June 30, 2024
• Study Completion: December 2, 2024
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)