Trial Outcomes & Findings for A Study of Tislelizumab (BGB-A317) Plus Chemoradiotherapy Followed by Tislelizumab Monotherapy in Newly Diagnosed, Stage III Subjects With Locally Advanced, Unresectable Non-small Cell Lung Cancer (NCT NCT03745222)

Results Overview

Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first. Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1 participants

Primary outcome timeframe

Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019

Results posted on

2020-07-15

Participant Flow

One participant was enrolled in the United States before the study was terminated.

Participant milestones

Participant milestones
Measure	Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of tislelizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) with concurrent chemoradiotherapy (cCRT), followed by monotherapy with tislelizumab 200 mg IV Q3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with tislelizumab 200 mg IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy - Placebo Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with placebo IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.
Overall Study STARTED	0	1	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of tislelizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) with concurrent chemoradiotherapy (cCRT), followed by monotherapy with tislelizumab 200 mg IV Q3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with tislelizumab 200 mg IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy - Placebo Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with placebo IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

A Study of Tislelizumab (BGB-A317) Plus Chemoradiotherapy Followed by Tislelizumab Monotherapy in Newly Diagnosed, Stage III Subjects With Locally Advanced, Unresectable Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of tislelizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) with concurrent chemoradiotherapy (cCRT), followed by monotherapy with tislelizumab 200 mg IV Q3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy -Tislelizumab n=1 Participants Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with tislelizumab 200 mg IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy - Placebo Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with placebo IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Total n=1 Participants Total of all reporting groups
Age, Categorical <=18 years	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	—	1 Participants n=7 Participants	—	1 Participants n=4 Participants
Age, Categorical >=65 years	—	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first. Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 5 years; date of randomization to date of death from any cause.

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Overall survival was defined as the time between randomization of treatment and death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Overall survival was defined as the time between randomization of treatment and death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Overall Response was defined as percentage of participants who had a radiologic confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines, between Day 1 of treatment and subsequent anti-cancer therapy, death or study discontinuation. Complete response was defined as the disappearance of all target lesions; partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease (PD).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Duration of Response is defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by blinded independent central review per RECIST v1.1, or death from any cause, whichever comes first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 18 months

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that is outside of the radiation field according to RECIST v1.1 or proven by biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days.

Population: Safety population includes participants who received at least 1 dose of study drug.

TEAEs include any adverse events (AEs) that had an onset date or a worsening in severity from baseline on or after the first dose of study drug up to 30 days following study drug discontinuation or initiation of new anticancer therapy, whichever occurred first. TEAEs also included all immune-related AEs recorded up to 90 days after the last dose of tislelizumab or placebo, regardless of whether or not the particpant started a new anticancer therapy. In addition, any serious AE with an onset date more than 30 days after the last dose of study drug that is assessed by the investigator as related to study drug were considered a TEAE."

Outcome measures

Outcome measures
Measure	Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of tislelizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) with concurrent chemoradiotherapy (cCRT), followed by monotherapy with tislelizumab 200 mg IV Q3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy -Tislelizumab n=1 Participants Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with tislelizumab 200 mg IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy - Placebo Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with placebo IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) ≥ 1 TEAE	—	1 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) ≥ 1 Treatment Related TEAE	—	1 Participants	—

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

The EORTC QLQ-C30 is a 30-item, questionnaire assessing quality of life (QoL), psychosocial burden and physical symptoms. It is classified into 15 domains: 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); each item is measured on a 4 point response scale; (not at all, a little, quite a bit, very much), with the exception of the 2 items measuring global health and QoL, (measured on a 7-point response scale). Scores are linearly transformed to 0 to 100 scores. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions; higher scores = better QoL, better functioning, or more severe symptoms, respectively. The LC13 covers 13 typical symptoms of lung cancer patients, such as coughing, pain, dyspnea, sore mouth, peripheral neuropathy, and hair loss.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 5 years

Population: The study was terminated. The number of participants and the data collection period were not sufficient for statistical analysis. The patient withdrew consent.

Included the percentage of participants who would have received at least one dose of tislelizumab or placebo in the monotherapy phase before progression.

Outcome measures

Outcome data not reported

Adverse Events

Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo + Concurrent Chemoradiotherapy -Tislelizumab

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo + Concurrent Chemoradiotherapy - Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tislelizumab + Concurrent Chemoradiotherapy -Tislelizumab Participants were to receive 2 cycles of tislelizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) with concurrent chemoradiotherapy (cCRT), followed by monotherapy with tislelizumab 200 mg IV Q3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy -Tislelizumab n=1 participants at risk Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with tislelizumab 200 mg IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.	Placebo + Concurrent Chemoradiotherapy - Placebo Participants were to receive 2 cycles of identically matching placebo by IV infusion Q 3 weeks with cCRT, followed by monotherapy with placebo IV Q 3W until disease progression, death, unacceptable toxicity, subject or physician decision, withdrawal of consent or treatment discontinuation for another reason.
Musculoskeletal and connective tissue disorders MUSCLE CRAMPING	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	100.0% 1/1 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,
Musculoskeletal and connective tissue disorders NECK PAIN	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	100.0% 1/1 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,
Respiratory, thoracic and mediastinal disorders Cough	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	100.0% 1/1 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,
Injury, poisoning and procedural complications Infusion Related Reaction	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	100.0% 1/1 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,	— 0/0 • From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days. No serious adverse events or deaths occurred during the course of the study,

Additional Information

Anne McClain

Celgene Corporation

Phone: 908-673-9100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER