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Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, ALCHEMIST Chemo-IO Study

Status
Active
Cancer Type
Lung Cancer
Trial Phase
Phase III
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT04267848
Protocol IDs
A081801 (primary)
A081801
NCI-2020-00751
Study Sponsor
Alliance for Clinical Trials in Oncology

Summary

This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for the treatment of stage IIA, IIB IIIA or IIIB non-small cell lung cancer that has been removed by surgery. 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. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel, 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. Giving pembrolizumab with usual chemotherapy may help increase survival times in patients with stage IIA, IIB IIIA or IIIB non-small cell lung cancer.

Objectives

PRIMARY OBJECTIVE:
I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

SECONDARY OBJECTIVES:
I. To compare the overall survival (OS) between the two treatment arms in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.
II. To compare the adverse event rates and drug discontinuation rates due to adverse events in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.
III. To compare the adverse event (AE) rates for Arms B and C with A (prior to Update #7) and estimate the DFS and OS in Arm A.
IV. To compare the DFS and OS in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer that receive at least 2 cycles of initial adjuvant chemotherapy.

QUALITY OF LIFE OBJECTIVES:
I. To compare patient-reported quality of life (QOL) one year after randomization as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core (C)30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B), and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C).
II. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC QLQ-C30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B) and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C).
III. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as assessed by the EORTC QLQ-Lung Cancer (LC13).

CORRELATIVE SCIENCE OBJECTIVES:
I. To compare the DFS and OS in the PD-L1 subgroup of patients with PD-L1 expression status (>= 1% vs < 1%).
II. To compare the DFS and OS by tumor mutational burden status (high vs. low) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (CLOSED AS OF UPDATE #7):
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then undergo observation.

ARM B:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles or every 6 weeks for 16 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.

ARM C:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity.

*ACCEPTABLE REGIMENS:
DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle.

DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle.

DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.

DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 of each cycle.

After completion of study treatment, patients are followed up at 6 weeks, then every 3 months for 2 years from randomization, every 6 months for years 2-4, and then annually for up to 10 years from randomization.

Eligibility

  1. Previously registered to A151216 (NCT02194738)
  2. Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only)
  3. Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only)
  4. Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263 * Note: Local testing results of EGFR and ALK by a local Clinical Laboratory Improvement Act (CLIA) certified laboratory is acceptable. The report must indicate the result as well as the CLIA number of the laboratory that performed the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, EIL3N or SP263 are acceptable for enrollment on A081801. Patients with local results for EGFR, ALK and PD-L1 still need to be registered to A151216 and follow all the submissions requirements but do NOT need to wait for the results to proceed to A081801 registration
  5. Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer (NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection). Patients will be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2017 * Note: Patients with pathologic N2 disease, completely resected, are eligible. However, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population
  6. Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery
  7. No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
  8. No prior allogeneic tissue/solid organ transplant
  9. No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
  10. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  11. Age >= 18 years
  12. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
  13. No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  14. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
  15. No patients with a “currently active” second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that have undergone potentially curative therapy are eligible
  16. No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  17. No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  18. No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
  19. Absolute neutrophil count (ANC) >= 1,500/mm^3
  20. Platelet count >= 100,000/mm^3
  21. Hemoglobin >= 8 gm/dl
  22. Calculated (Calc.) creatinine clearance >= 45 mL/min
  23. Total bilirubin =< 1.5 x upper limit of normal (ULN)
  24. Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Treatment Sites in Georgia

Atlanta Cancer Care - Alpharetta


3400 C Old Milton Parkway
Suite 400
Alpharetta, GA 30005
770-777-1315
www.atlantacancercare.com

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
770-205-5292 x1041
www.atlantacancercare.com

Atlanta Cancer Care - Decatur


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

Atlanta Cancer Care - Stockbridge


7813 Spivey Station Boulevard
Suite 210
Jonesboro, GA 30236
678 466-2069
www.atlantacancercare.com

Atlanta Cancer Care - Tower


5670 Peachtree Dunwoody Road
Suite 1100
Atlanta, GA 30342
404-303-3355
www.atlantacancercare.com

Atlanta Gynecologic Oncology


980 Johnson Ferry Road
Suite 900
Atlanta, GA 30342
404-303-3355
www.geraldfeuer.com

Georgia Cancer Specialists - Athens


125 King Avenue
Suite 200
Athens, GA 30606
www.gacancer.com

Georgia Cancer Specialists - Canton


228 Riverstone Drive
Canton, GA 30114
www.gacancer.com

Georgia Cancer Specialists - CenterPointe


1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com

Georgia Cancer Specialists - Kennestone


790 Church Street
Suite 335
Marietta, GA 30060
www.gacancer.com

Georgia Cancer Specialists - Macon-Coliseum


308 Coliseum Drive
Suite 120
Macon, GA 31217
478-745-6130 x8152
www.gacancer.com

Georgia Cancer Specialists - Stemmer


2712 Lawrenceville Highway
Decatur, GA 30033
770-496-5555
www.gacancer.com

Georgia Gynecologic Oncology


980 Johnson Ferry Road
Suite 910
Atlanta, GA 30342
404-303-3355
www.ggo-atl.com/

Northside Hospital Cancer Institute


1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-303-3355
www.northside.com

Northside Hospital Cancer Institute - Forsyth


1200 Northside Forsyth Drive
Suite 140
Cumming, GA 30041
404-303-3355
www.northside.com

University Gynecologic Oncology


960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
404-303-3355
www.ugynonc.com

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
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