Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Davis
Dates
study started
estimated completion
Principal Investigator
Karen L. Kelly (ucdavis)

Description

Summary

This phase III ALCHEMIST trial compares the addition of pembrolizumab to usual chemotherapy versus usual chemotherapy for the treatment of stage IB, II, or IIIA 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. Drugs used in chemotherapy, 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. The purpose of this trial is to find out if the addition of pembrolizumab to usual chemotherapy is better or worse than usual chemotherapy alone for non-small cell lung cancer.

Official Title

Integration of Immunotherapy Into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO

Details

PRIMARY OBJECTIVES:

  1. To compare the disease free survival (DFS) and overall survival (OS) (dual primary endpoints) between combination MK-3475 (pembrolizumab) plus standard of care (Arm C) versus (vs.) standard of care (Arm A) in patients with stage IB-IIIA non-small cell lung cancer.

II. To compare the DFS and OS (dual primary endpoints) between sequential MK-3475 (pembrolizumab) following standard of care (Arm B) vs. standard of care (Arm A) followed by observation in patients with stage IB-IIIA non-small cell lung cancer.

SECONDARY OBJECTIVES:

  1. To compare the DFS and OS between combination MK-3475 (pembrolizumab) with standard of care (Arm C) vs. sequential standard of care followed by MK-3475 (pembrolizumab) (Arm B) in patients with stage IB-IIIA non-small cell lung cancer.

II. To compare the adverse event rates and drug discontinuation rates due to adverse events with the addition of MK-3475 (pembrolizumab) plus standard of care (combination and/or sequential; Arms B and C) vs. standard of care alone (Arm A) as well as Arm B versus Arm C in patients with stage IB-IIIA non-small cell lung cancer.

III. To compare the DFS and OS between MK-3475 (pembrolizumab) plus standard of care (combination and/or sequential; Arms B and C) vs. standard of care alone (Arm A) by PD-L1 expression status (>= 50% vs < 50%) in patients with stage IB-IIIA non-small cell lung cancer.

IV. To compare the DFS and OS between MK-3475 (pembrolizumab) plus standard of care (combination and/or sequential; Arms B and C) vs. standard of care alone (Arm A) in patients with stage IB-IIIA non-small cell lung cancer that receive at least 2 cycles of initial adjuvant chemotherapy.

QUALITY OF LIFE OBJECTIVES:

  1. 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 MK-3475 (pembrolizumab) (Arm B), and those randomized to receive adjuvant chemotherapy + observation (Arm A).

II. To compare patient reported QOL one year after randomization as assessed by EORTC QLQ-C30 between patients randomized to receive adjuvant chemotherapy + MK-3475 (pembrolizumab) concomitantly (Arm C) and those randomized to receive adjuvant chemotherapy + observation (Arm A).

III. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC QLQ-C30 between patients randomized to receive adjuvant chemotherapy + MK-3475 (pembrolizumab) concomitantly (Arm C) and those randomized to receive adjuvant chemotherapy + observation or adjuvant chemotherapy followed by MK-3475 (pembrolizumab) (Arms A and B combined).

IV. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as assessed by the EORTC QLQ-Lung Cancer (LC13).

CORRELATIVE SCIENCE OBJECTIVES:

  1. To compare the DFS and OS with the addition of MK-3475 (pembrolizumab) (combination and/or sequential) to standard of care platinum-based adjuvant therapy (Arms B and C) vs standard of care (Arm A) in the PD-L1 subgroup of patients with PD-L1 expression status (>= 1% vs < 1%).

II. To compare the DFS and OS with the addition of MK-3475 (pembrolizumab) (combination and/or sequential) to standard of care platinum-based adjuvant therapy (Arms B and C) vs. standard of care (Arm A) by tumor mutational burden status (high vs. low) in patients with stage IB-IIIA non-small cell lung cancer.

III. To identify a cell-free deoxyribonucleic acid (cfDNA) marker associated with high-risk of recurrence and improved DFS and OS with the addition of MK-3475 (pembrolizumab) to standard adjuvant chemotherapy (Arms B and C).

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A:

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 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 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.

Keywords

Lung Non-Small Cell Carcinoma Stage IB Lung Cancer AJCC v7 Stage II Lung Cancer AJCC v7 Stage IIA Lung Cancer AJCC v7 Stage IIB Lung Cancer AJCC v7 Stage IIIA Lung Cancer AJCC v7 Lung Neoplasms Carcinoma, Non-Small-Cell Lung Gemcitabine Paclitaxel Cisplatin Carboplatin Pembrolizumab Albumin-Bound Paclitaxel Pemetrexed Gemcitabine Hydrochloride Observation Pemetrexed Disodium Quality-of-Life Assessment

Eligibility

For people ages 18 years and up

Inclusion Criteria:

  • Previously registered to A151216
  • Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation
  • Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative)
  • Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, 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, 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
  • Completely resected stage IB (>= 4 cm), II or IIIA non-small cell lung cancer (NSCLC) with negative margins (complete R0 resection). Patients will be staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2010
  • 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
  • Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery
  • No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
  • No prior allogeneic tissue/solid organ transplant
  • Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
  • No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
  • 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
  • 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
  • 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
  • No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • 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
  • 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
  • Absolute neutrophil count (ANC) >= 1,500/mm3

  • Platelet count >= 100,000/mm3

  • Hemoglobin >= 8 gm/dl
  • Calculated (Calc.) creatinine clearance >= 45 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • Sutter Davis Hospital accepting new patients
    Davis California 95616 United States
  • California Pacific Medical Center-Pacific Campus accepting new patients
    San Francisco California 94115 United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center accepting new patients
    Burbank California 91505 United States
  • Bay Area Breast Surgeons Inc accepting new patients
    Emeryville California 94608 United States
  • Epic Care Partners in Cancer Care accepting new patients
    Emeryville California 94608 United States
  • Alta Bates Summit Medical Center - Summit Campus accepting new patients
    Oakland California 94609 United States
  • Bay Area Tumor Institute accepting new patients
    Oakland California 94609 United States

Lead Scientist at UC Health

  • Karen L. Kelly (ucdavis)
    Professor, Hematology and Oncology. Authored (or co-authored) 165 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Cancer Institute (NCI)
ID
NCT04267848
Phase
Phase 3
Study Type
Interventional
Last Updated