GA NCORP

NCORP Trials

Testing the Timing of Pembrolizumab Alone or With Chemotherapy as First Line Treatment and Maintenance in Non-small Cell Lung Cancer

Status
Active
Cancer Type
Lung Cancer
Trial Phase
Phase III
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCD ID
NCT03793179
Protocol IDs
EA5163 (primary)
EA5163
NCI-2018-03695
Study Sponsor
ECOG-ACRIN Cancer Research Group

Summary

This phase III trial studies whether pembrolizumab alone as a first-line treatment, followed by pemetrexed and carboplatin with or without pembrolizumab after disease progression is superior to induction with pembrolizumab, pemetrexed and carboplatin followed by pembrolizumab and pemetrexed maintenance in treating patients with stage IV non-squamous non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving first-line pembrolizumab followed by pemetrexed and carboplatin with or without pembrolizumab works better in treating patients with non-squamous non-small cell cancer.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate overall survival (OS) in each of the 2 experimental arms (Arms A and B) to control (Arm C).

SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Arm C versus each of Arms A and B.
II. To evaluate best objective response rates per RECIST 1.1 for Arm C versus each of Arms A and B.
III. To estimate toxicity within each of the treatment arms via the Common Terminology Criteria for Adverse Events (CTCAE) criteria.
IV. To compare outcomes between Arms A and B.
V. To compare outcomes by treatment arm within subgroups defined by a cutpoint of PD-L1 expression at >= 50%.

BIOMARKER OBJECTIVE:
I. To collect and bank tissue and blood for future research studies, including potential development of a prognostic and predictive signature for MK-3475 (pembrolizumab) in combination with chemotherapy versus MK-3475 (pembrolizumab) alone.

EXPLORATORY IMAGING OBJECTIVES:
I. To collect and bank standard of care computed tomography (CT) imaging at baseline and first three follow-up post-treatment scans for developing the radiomic risk score with the following exploratory objectives:
Ia. Validate the Radiomic Risk score on pre-treatment scans as well as compute differences between pre- and post- treatment scans (delta features) in determining which patients will benefit from first line pembrolizumab in the metastatic setting in both low (< 50%) and high (> 50%) PD-L1 cohorts using patients in Arm 1 and Arm 2 of the trial where pembrolizumab is used as first line treatment.
Ib. To use the Radiomic Risk score in order to predict which patients would benefit from combination pembrolizumab and subsequent chemotherapy vs. immunotherapy alone in both low (< 50%) and high (> 50%) PD-L1 cohorts using patients who went on to receive chemotherapy as second line and stratifying the patients based on those who received benefit from pembrolizumab plus chemotherapy versus (vs.) pembrolizumab alone.
Ic. Exploratory analysis for other radiomic profiles in predicting response.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pemetrexed IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then may receive pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 6 weeks of disease progression, patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.

ARM C: Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every 21 days for up to 2 years for pembrolizumab in the absence of disease progression or unacceptable toxicity and until to disease progression for pemetrexed.

After completion of study treatment, patients are followed up for 5 years.

Treatment Sites


Atlanta Cancer Care - Alpharetta
3400 C Old Milton Parkway
Suite 400
Alpharetta, GA 30005
Kristin Sieverding
770-777-1315
www.atlantacancercare.com

Doctors:

Colleen S. Austin MD
Silpa C. Reddy MD
Sreekanth C. Reddy MD
Ronald G. Steis MD

Atlanta Cancer Care - Conyers
1498 Klondike Road
Suite 106
Conyers, GA 30094
404-303-3355
www.atlantacancercare.com

Atlanta Cancer Care - Cumming
1505 Northside Boulevard
Suite 4600
Cumming, GA 30041
Renee Gaiter
770-205-5292 x1041
www.atlantacancercare.com

Doctors:

Sreekanth C. Reddy MD
Ronald G. Steis MD
Amelia B. Zelnak MD
Kelly A. May MD

Atlanta Cancer Care - Decatur
2545 Lawrenceville Highway
Suite 300
Decatur, GA 30033
404-303-3355
www.atlantacancercare.com

Doctors:

Lijo Simpson MD

Atlanta Cancer Care - Stockbridge
7813 Spivey Station Boulevard
Suite 210
Jonesboro, GA 30236
Andrena Jefferson
678 466-2069
www.atlantacancercare.com

Doctors:

Gurinderjit K. Sidhu MD
Lijo Simpson MD

Georgia Cancer Specialists - Athens
125 King Avenue
Suite 200
Athens, GA 30606
Cynthia Pirkle
www.gacancer.com

Doctors:

Ranjana S. Bhargava MD
Priya Rudolph

Georgia Cancer Specialists - CenterPointe
1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
Anila Lokhandwala
404-256-4777 ext 9242
www.gacancer.com

Doctors:

Rodolfo E. Bordoni MD
Pradeep C. Jolly MD

Georgia Cancer Specialists - Macon-Coliseum
308 Coliseum Drive
Suite 120
Macon, GA 31217
Sonia Hernandez
478-745-6130 x8152
www.gacancer.com