M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC)

Conditions

Non-small Cell Lung Cancer

Keywords

M7824, Pembrolizumab, PD-L1-tumor Expression, INTR@PID Lung 037, Bintrafusp alfa

Brief summary

The purpose of the study is to evaluate the efficacy and safety of bintrafusp alfa (M7824) compared with pembrolizumab in participants with advanced NSCLC with high PD-L1-tumor expression, with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. The Phase III adaptive design allows for the option to recruit up to 584 patients based on pre-specified rules.

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Abstract 6179: Machine learning (ML)-spatial quantification of the tumor microenvironment (TME) identifies differences associated with response to bintrafusp alfa (BA) <i>vs</i> pembrolizumab (PEM) treatment in the Phase 3 INTR@PID Lung 037 study

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Randomized open-label study of M7824 versus pembrolizumab as first-line (1L) treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC).

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Randomized open-label study of M7824 versus pembrolizumab as first-line (1L) treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC).

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Interventions

DRUGM7824

Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

DRUGPembrolizumab

Pembrolizumab: Participants received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Histologically confirmed diagnosis of advanced NSCLC * Have not received prior systemic therapy treatment for their advanced/Stage four NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy, and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease. Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant chemotherapy therapy to Grade less than or equal to 1. For radiation toxicity or prior major surgeries, participants should have recovered from side effects and/or complications * Have measurable disease based on RECIST 1.1 * Have a life expectancy of at least 3 months * Availability of tumor tissue (less than 6 months old) before the first dose is mandatory to determine PD-L1 expression level prior to enrollment * PD-L1 high status as determined by central testing * Other protocol defined inclusion criteria could apply

Exclusion criteria

* Participants with nonsquamous NSCLC histologies whose tumor harbors any of the following molecular alterations and targeted therapy is locally approved: epidermal growth factor receptor (EGFR) sensitizing (activating) mutation, anaplastic lymphoma kinase (ALK) translocation, ROS1 rearrangement, or BRAF V600E mutation * Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic radiation therapy of greater than 30 units of gray (Gy) within 6 months prior to the first dose of study * Known severe hypersensitivity to investigational products (M7824 or pembrolizumab), or any components in their formulations * Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years * Other protocol defined

Design outcomes

Primary

Measure	Time frame	Description
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days	Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Overall Survival (OS)	Time from randomization of study drug assessed approximately up to 843 days	Overall Survival was defined as the time from randomization of study intervention to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.

Secondary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Time from first treatment assessed up to approximately 843 days	Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention.
Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days	Percentage of participants with unconfirmed best overall response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here.
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days	DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.

Countries

Argentina, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States

Participant flow

Participants by arm

Arm	Count
M7824 Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.	152
Pembrolizumab Participants received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.	152
Total	304

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Randomized, not treated	1	0

Baseline characteristics

Characteristic	Pembrolizumab	Total	M7824
Age, Continuous	67 Years STANDARD_DEVIATION 10.17	67 Years STANDARD_DEVIATION 9.85	67 Years STANDARD_DEVIATION 9.56
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants	24 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	138 Participants	276 Participants	138 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants	4 Participants	1 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	55 Participants	105 Participants	50 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	4 Participants	7 Participants	3 Participants
Race/Ethnicity, Customized Unknown or Not Reported	14 Participants	21 Participants	7 Participants
Race/Ethnicity, Customized White	79 Participants	170 Participants	91 Participants
Sex: Female, Male Female	36 Participants	78 Participants	42 Participants
Sex: Female, Male Male	116 Participants	226 Participants	110 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	49 / 151	43 / 152
other Total, other adverse events	140 / 151	135 / 152
serious Total, serious adverse events	90 / 151	61 / 152

Outcome results

Primary

Overall Survival (OS)

Overall Survival was defined as the time from randomization of study intervention to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.

Time frame: Time from randomization of study drug assessed approximately up to 843 days

Population: Full analysis set included all participants who were randomized to study intervention.

Arm	Measure	Value (MEDIAN)
M7824	Overall Survival (OS)	21.1 months
Pembrolizumab	Overall Survival (OS)	22.1 months

Primary

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Time frame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days

Population: Full analysis set included all participants who were randomized to study intervention.

Arm	Measure	Value (MEDIAN)
M7824	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	7.0 months
Pembrolizumab	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	11.1 months

Secondary

Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.

Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days

Population: Full analysis set included all participants who were randomized to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
M7824	Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	NA months
Pembrolizumab	Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	NA months

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention.

Time frame: Time from first treatment assessed up to approximately 843 days

Population: Safety analysis set included all participants who were administered at least one dose of M7824 or Pembrolizumab.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M7824	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any TEAE	150 Participants
M7824	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any serious TEAE	90 Participants
M7824	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any Treatment Related TEAEs	124 Participants
Pembrolizumab	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any TEAE	145 Participants
Pembrolizumab	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any serious TEAE	61 Participants
Pembrolizumab	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Participants with any Treatment Related TEAEs	105 Participants

Secondary

Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

Percentage of participants with unconfirmed best overall response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here.

Time frame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days

Population: Full analysis set included all participants who were randomized to study intervention.

Arm	Measure	Value (NUMBER)
M7824	Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	46.7 percentage of participants
Pembrolizumab	Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	51.3 percentage of participants

M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC)

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Overall Survival (OS)

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)