Clinical Trial: NCT04380636 - My Cancer Genome

NCT04380636

Description:

The purpose of this study is to assess the efficacy and safety of pembrolizumab in combination with concurrent chemoradiation therapy followed by either pembrolizumab with olaparib placebo (Arm 1) or with olaparib (Arm 2) compared to concurrent chemoradiation therapy followed by durvalumab (Arm 3) in participants with unresectable, locally advanced NSCLC. Arms 1 and 2 will be studied in a double-blind design and Arm 3 will be open-label. The primary hypotheses are: 1. Pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with olaparib is superior to concurrent chemoradiation therapy followed by durvalumab with respect to progression-free survival (PFS) and overall survival (OS) 2. pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab is superior to concurrent chemoradiation therapy followed by durvalumab with respect to PFS and OS

Related Conditions:

Non-Small Cell Lung Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04380636

Trial Eligibility

Document

Title

Brief Title: Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012)
Official Title: A Phase 3 Study of Pembrolizumab (MK-3475) in Combination With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib vs Concurrent Chemoradiation Therapy Followed by Durvalumab in Participants With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

ORG STUDY ID: 7339-012
SECONDARY ID: 2019-003237-41
SECONDARY ID: MK-7339-012
SECONDARY ID: KEYLYNK-012
SECONDARY ID: 205352
NCT ID: NCT04380636

Conditions

Lung Neoplasms
Carcinoma, Non-Small-Cell Lung

Interventions

Drug	Synonyms	Arms
Pembrolizumab	KEYTRUDA®, MK-3475	pembrolizumab+chemoradiation→pembrolizumab+olaparib
Olaparib	LYNPARZA®, MK-7339, AZD2281, KU-0059436	pembrolizumab+chemoradiation→pembrolizumab+olaparib
Placebo for olaparib		pembrolizumab+chemoradiation→pembrolizumab+olaparib placebo
Etoposide	VEPESID®	chemoradiation→durvalumab
Carboplatin	PARAPLATIN®	chemoradiation→durvalumab
Cisplatin	PLATINOL®	chemoradiation→durvalumab
Paclitaxel	TAXOL®	chemoradiation→durvalumab
Pemetrexed	ALIMTA®	chemoradiation→durvalumab
Durvalumab	IMFINZI®	chemoradiation→durvalumab

Purpose

Trial Arms

Name	Type	Description	Interventions
pembrolizumab+chemoradiation→pembrolizumab+olaparib placebo	Experimental	Participants will receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) in combination with 3 cycles of the investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gray (Gy) over 6 weeks) followed by pembrolizumab plus olaparib placebo twice a day (BID) for approximately 1 year.	Pembrolizumab Placebo for olaparib Etoposide Carboplatin Cisplatin Paclitaxel Pemetrexed
pembrolizumab+chemoradiation→pembrolizumab+olaparib	Experimental	Participants will receive pembrolizumab 200 mg IV Q3W in combination with 3 cycles of the investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gy over 6 weeks) followed by pembrolizumab plus olaparib 300 mg BID for approximately 1 year.	Pembrolizumab Olaparib Etoposide Carboplatin Cisplatin Paclitaxel Pemetrexed
chemoradiation→durvalumab	Active Comparator	Participants will receive 3 cycles of the investigator's choice of platinum doublet chemotherapy with concurrent standard thoracic radiotherapy (60 Gy over 6 weeks) followed by durvalumab 10 mg/kg every 2 weeks (Q2W) for approximately 1 year.	Etoposide Carboplatin Cisplatin Paclitaxel Pemetrexed Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC

          -  Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8

          -  Is unable to undergo surgery with curative intent for Stage III NSCLC

          -  Has no evidence of metastatic disease indicating Stage IV NSCLC

          -  Has measurable disease as defined by RECIST 1.1

          -  Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for
             Stage III NSCLC; participants who have received neoadjuvant and/or adjuvant therapy
             for early stage disease are not eligible

          -  Has provided a tumor tissue sample (tissue biopsy [core, incisional, or excisional])

          -  Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 assessed
             within 7 days prior to the first administration of study intervention

          -  Has a life expectancy of at least 6 months

          -  A male participant must agree to use contraception and refrain from donating sperm
             during the intervention period and for at least the time needed to eliminate each
             study intervention after the last dose of study intervention. The length of time
             required to continue contraception for each study intervention is as follows: Olaparib
             and platinum doublet: 90 days

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and agrees to use contraception and refrain from donating eggs (ova,
             oocytes) to others or freeze/store for her own use for the purpose of reproduction
             during the treatment period and for at least the time needed to eliminate each study
             intervention after the last dose of study intervention. The length of time required to
             continue contraception for each study intervention is as follows: Pembrolizumab: 120
             days Olaparib and platinum doublet: 180 days

          -  Has a negative highly sensitive pregnancy test ([urine or serum] as required by local
             regulations) within 24 hours for urine or within 72 hours for serum before the first
             dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an
             ambiguous result), a serum pregnancy test is required. In such cases, the participant
             must be excluded from participation if the serum pregnancy result is positive.

          -  Has had her medical history, menstrual history, and recent sexual activity reviewed by
             the investigator to decrease the risk for inclusion of a woman with an early
             undetected pregnancy.

          -  Has adequate pulmonary function tests

          -  Has adequate organ function

          -  Has provided written informed consent

        Exclusion Criteria:

          -  Has small cell lung cancer or a mixed tumor with presence of small cell elements

          -  Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features
             suggestive of MDS/AML

          -  Has had documented weight loss >10% (from baseline) in the preceding 3 months

          -  Has received prior radiotherapy to the thorax, including radiotherapy to the
             esophagus, mediastinum, or for breast cancer

          -  Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1),
             anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death
             ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or
             co-inhibitory T-cell receptor

          -  Has received prior therapy with olaparib or with any other polyadenosine
             5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor

          -  Has had major surgery <4 weeks prior to the first dose of study treatment (except for
             placement of vascular access)

          -  Is expected to require any other form of antineoplastic therapy, while on study

          -  Has received a live or live attenuated vaccine within 30 days before the first dose of
             study intervention; administration of killed vaccines is allowed

          -  Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
             [GCSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant
             erythropoietin) within 28 days prior to the first dose of study treatment

          -  Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
             moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be
             discontinued for the duration of the study

          -  Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin,
             protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir,
             nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin,
             diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot
             be discontinued for the duration of the study

          -  Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs),
             other than an aspirin dose ≤1.3 grams per day, for at least 2 days before, during, and
             for at least 2 days after administration of pemetrexed

          -  Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone during
             administration of pemetrexed

          -  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 treatment

          -  The presence of uncontrolled, potentially reversible cardiac conditions, as judged by
             the investigator or has congenital long QT syndrome

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior the first dose of
             study intervention

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 5 years with the exception of basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ
             (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially
             curative therapy

          -  Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of its
             excipients

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years

          -  Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
             steroids or has current pneumonitis/interstitial lung disease

          -  Has an active infection requiring systemic therapy

          -  Has a known history of human immunodeficiency virus (HIV) infection

          -  Has a known history of Hepatitis B or known active Hepatitis C virus infection

          -  Has active tuberculosis (TB; Mycobacterium tuberculosis) and is receiving treatment

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the participant's
             participation for the full duration of the study, or is not in the best interest of
             the participant to participate, in the opinion of the treating investigator

          -  Is considered a poor medical risk due to a serious, uncontrolled medical disorder or
             nonmalignant systemic disease in the opinion of the treating investigator

          -  Has a known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the study

          -  Is unable to swallow orally administered medication or has a gastrointestinal disorder
             affecting absorption

          -  Has had an allogenic tissue/solid organ transplant

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame:	Up to approximately 48 months
Safety Issue:
Description:	PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Measure:	Incidence of Adverse Events (AE)
Time Frame:	Up to approximately 72 months
Safety Issue:
Description:	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Measure:	Discontinuation Rate of Study Intervention Due to an Adverse Event (AE)
Time Frame:	Up to approximately 72 months
Safety Issue:
Description:	An AE is defined as as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Measure:	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame:	Up to approximately 72 months
Safety Issue:
Description:	ORR is defined as the percentage of participants who have achieved a Complete Response (CR) or a Partial Response (PR).

Measure:	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame:	Up to approximately 72 months
Safety Issue:
Description:	DOR is defined as the time from first documented evidence of Complete Response (CR) or a Partial Response (PR) until disease progression or death due to any cause, whichever occurs first.

Measure:	Change from Baseline in EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score
Time Frame:	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Safety Issue:
Description:	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scale scores will be presented.

Measure:	Change From Baseline in Cough Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) Item 1 Score
Time Frame:	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Safety Issue:
Description:	The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for cough (Item 1). For this item, individual responses to the question "How much did you cough?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 cough scale score will be presented.

Measure:	Change From Baseline in Chest Pain Using the EORTC QLQ-LC13 Item 10 Score
Time Frame:	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Safety Issue:
Description:	The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for chest pain (Item 10). For this item, individual responses to the question "Have you had pain in your chest?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 chest pain scale score will be presented.

Measure:	Change From Baseline in Dyspnea Using the EORTC QLQ-C30 Item 8 Score
Time Frame:	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Safety Issue:
Description:	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients and includes a single-item scale score for dyspnea (Item 8). Participant responses to the question "Were you short of breath? are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 dyspnea scale score will be presented.

Measure:	Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score
Time Frame:	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Safety Issue:
Description:	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The physical functioning scale consists of participant responses to 5 questions regarding performance of daily activities [1) strenuous activities; 2) long walks; 3) short walks; 4) bed/chair rest; and 5) needing help with eating, dressing, washing themselves or using the toilet]. Participant responses are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a higher score indicating a better quality of life. The change from baseline in the EORTC QLQ-C30 physical functioning scale score will be presented.

Measure:	Time to Deterioration (TTD) in HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Score
Time Frame:	Up to approximately 72 months post randomization
Safety Issue:
Description:	TTD is defined as the time to first onset of a ≥10-point decrease from baseline for EORTC QLQ-C30 Items 29 and 30 scale scores. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.

Measure:	TTD in Cough Using the EORTC QLQ-LC13 Item 1 Score
Time Frame:	Up to approximately 72 months post randomization
Safety Issue:
Description:	TTD is defined as the time to first onset of a ≥10-point decrease from baseline for EORTC QLQ-LC13 Item 1 scale score. The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for cough (Item 1). For this item, individual responses to the question "How much did you cough?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome.

Measure:	TTD in Chest Pain Using the EORTC QLQ-LC13 Item 10 Score
Time Frame:	Up to approximately 72 months post randomization
Safety Issue:
Description:	TTD is defined as the time to first onset of a ≥10-point decrease from baseline for EORTC QLQ-LC13 Item 10 scale score. The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for chest pain (Item 10). For this item, individual responses to the question "Have you had pain in your chest?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome.

Measure:	TTD in Dyspnea Using the EORTC QLQ-C30 Item 8 Score
Time Frame:	Up to approximately 72 months post randomization
Safety Issue:
Description:	TTD is defined as the time to first onset of a ≥10-point decrease from baseline for EORTC QLQ-C30 Item 8 scale score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients and includes a single-item scale score for dyspnea (Item 8). Participant responses to the question "Were you short of breath? are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome.

Measure:	TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score
Time Frame:	Up to approximately 72 months post randomization
Safety Issue:
Description:	TTD is defined as the time to first onset of a ≥10-point decrease from baseline for EORTC QLQ-C30 Items 1-5 scale scores. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The physical functioning scale consists of participant responses to 5 questions regarding performance of daily activities [1) strenuous activities; 2) long walks; 3) short walks; 4) bed/chair rest; and 5) needing help with eating, dressing, washing themselves or using the toilet]. Participant responses are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a higher score indicating a better quality of life.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Merck Sharp & Dohme Corp.

Trial Keywords

Programmed Cell Death Receptor 1 (PD-1, PD1)
Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1)
Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)
polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor

Last Updated

August 26, 2021

Clinical Trials /

Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012)