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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, an ALCHEMIST Treatment Trial (Chemo-IO [ACCIO])

ConditionsLung Non-Small Cell CarcinomaLung Non-Small Cell Squamous CarcinomaLung Non-Squamous Non-Small Cell CarcinomaStage II Lung Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase III ALCHEMIST treatment 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Has not undergone a hysterectomy or bilateral oophorectomy; or

Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only)

Local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only)

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Carboplatin

    Drug

    Given IV

  • Cisplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Gemcitabine Hydrochloride

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Observation Activity

    Other intervention

    Undergo observation

  • Paclitaxel

    Drug

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Pemetrexed Disodium

    Drug

    Given IV

  • Questionnaire Administration

    Other intervention

    Ancillary studies

Treatment groups

1,210 Participants
are divided into 3 treatment groups
Group A: Arm A (platinum doublet, observation)Active comparator 11 interventions
Group B: Arm B (platinum doublet, sequential pembrolizumab)Experimental treatment 11 interventions
Group C: Arm C (platinum doublet, combination pembrolizumab)Experimental treatment 11 interventions

Trial outcomes

Primary outcomes

1

Disease free survival (DFS)

Will compare DFS between the two arms (combination versus sequential pembrolizumab added to standard of care platinum-based adjuvant therapy) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. Will be estimated using the Kaplan-Meier method, where the stratified log-rank test (using the central PD-L1 result for the PD-L1 expression status) will be used to compare the distributions across the treatment arms. DFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors (using the central PD-L1 result for the PD-L1 expression status) used in the randomization will be assessed as well.

Time frame
From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion

Secondary outcomes

1

Overall survival (OS)

Will be estimated using the Kaplan-Meier method, where the stratified log-rank test (using the central PD-L1 result for the PD-L1 expression status) will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors (using the central PD-L1 result for the PD-L1 expression status) used in the randomization will be assessed as well.

Time frame
From randomization to death from any cause, assessed up to completion of 5 years follow-up
2

Incidence of adverse events

The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5. will compare the adverse event rates and drug discontinuation rates due to adverse events. To evaluate the adverse events profiles associated with each treatment arm, the maximum grade for each type of adverse event will be recorded for each patient and frequency tables will be reviewed to determine the overall patterns. The number and severity of grade 3 + adverse events will be tabulated and summarized. Analysis of the overall adverse event rates, as well as specific events of interest will involve chi-square tests or Fisher's exact tests. In addition, we will also compute and compare the total adverse event burden for each arm

Time frame
Up to 10 years
3

DFS between each of the arms

Will compare the DFS by PD-L1 expression status (tumor proportion score \[TPS\] ≥ 50% versus \[vs\] TPS \< 50% using the central PD-L1 expression status) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. This will be assessed using the treatment arm by PD-L1 expression status (using the central PD-L1 expression status) interaction effect on DFS. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models. Similar analyses will be performed for the correlative endpoints using the cut off of 1% for the PD-L1 expression status (using the central PD-L1 expression status), and tumor mutational burden (high vs low).

Time frame
From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion
4

OS between each of the arms

will compare the OS by PD-L1 expression status (TPS ≥ 50% vs TPS \< 50% using the central PD-L1 expression status) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. This will be assessed using the treatment arm by PD-L1 expression status (using the central PD-L1 expression status) interaction effect on OS. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models. Similar analyses will be performed for the correlative endpoints using the cut off of 1% for the PD-L1 expression status (using the central PD-L1 expression status), and tumor mutational burden (high vs low).

Time frame
From randomization to death from any cause, assessed up to completion of 5 years of follow-up

Other outcomes

1

Patient-reported quality of life (QOL)

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). All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. Will be summarized descriptively for patients randomized to receive adjuvant chemotherapy + observation (Arm A). Correlation analysis and logistic regression analysis will be used to examine whether baseline patient characteristics and prognostic factors predict missingness.

Time frame
Up to 1 year after randomization
2

Patient-reported QOL

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).All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. Will be summarized descriptively for patients randomized to receive adjuvant chemotherapy + observation (Arm A). Correlation analysis and logistic regression analysis will be used to examine whether baseline patient characteristics and prognostic factors predict missingness.

Time frame
Up to completion of chemotherapy
3

Patient-reported dyspnea and coughing

Assessed by the EORTC QLQ-Lung Cancer 13. All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. Will be summarized descriptively for patients randomized to receive adjuvant chemotherapy + observation (Arm A). Correlation analysis and logistic regression analysis will be used to examine whether baseline patient characteristics and prognostic factors predict missingness.

Time frame
Up to 2 years after randomization

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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