Trial Outcomes & Findings for A BRIDGING STUDY OF PF-06439535 (CN) PLUS PACLITAXEL-CARBOPLATIN VERSUS BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN IN NSCLC (NCT NCT04325698)

Last Updated: 2024-10-01

Results Overview

Objective response referred to complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (non-progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions, normal nodes (target nodes must decrease to normal size); PR: \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

8 participants

Primary outcome timeframe

From Week 1 to Week 25 (25 Weeks)

Results posted on

2024-10-01

Participant Flow

The study was terminated on 17 March 2021 by the Sponsor. This study was conducted in China.

A total of 13 participants were screened, of which 5 were screen failure. Four participants were randomized into each of the PF-06439535 (CN) or bevacizumab (EU) groups. Sample size after termination is very small. To avoid the risk of participant re-identification, participant flow was reported in a single overall study period.

Participant milestones

Participant milestones
Measure	PF-06439535 (CN) Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of area under the concentration versus time curve \[AUC\] 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via intravenous (IV) infusion in order on 21-day cycles.	Bevacizumab (EU) Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.
Overall Study STARTED	4	4
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-06439535 (CN) Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of area under the concentration versus time curve \[AUC\] 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via intravenous (IV) infusion in order on 21-day cycles.	Bevacizumab (EU) Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.
Overall Study Study Terminated By Sponsor	1	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

A BRIDGING STUDY OF PF-06439535 (CN) PLUS PACLITAXEL-CARBOPLATIN VERSUS BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN IN NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-06439535 (CN) n=4 Participants Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21 day cycles.	Bevacizumab (EU) n=4 Participants Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.	Total n=8 Participants Total of all reporting groups
Age, Customized	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants
Sex: Female, Male Female	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants
Sex: Female, Male Male	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Week 1 to Week 25 (25 Weeks)

Population: The Intent-to-treat (ITT) population was defined as all participants who were randomized to study treatment. Data for analyzing endpoint were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 to end of Cycle 8; 1 Cycle = 21 Days

Population: The safety population was defined as all participants who were randomized and received at least one dose of investigational product.

TEAE was defined as any adverse event that occurs after the beginning of the investigational product or any pre-existing adverse event (AE) that worsens after the beginning of the investigational product. Serious adverse events (SAE) were assessed by the investigator. Severity of AE was graded based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3-SEVERE AE; Grade 4-LIFE-THREATENING consequences; urgent intervention indicated; Grade 5-DEATH RELATED TO AE.

Outcome measures

Outcome measures
Measure	PF-06439535 (CN) n=4 Participants Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21 day cycles.	Bevacizumab (EU) n=4 Participants Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with all causalities AEs	4 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with all causalities SAEs	1 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with all causalities AEs of maximum grade 3 or 4	2 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with all causalities AEs of maximum grade 5	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs	4 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related SAEs	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs of maximum grade 3 or 4	1 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Treatment Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs of maximum grade 5	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 1 Cycle = 21 Days

Population: All participants who were randomized and received at least 1 dose of investigational product were used for ADA and neutralizing antibody (NAb) analyses. The number of participants analyzed are those numbers with participants ADA samples tested.

ADA have been evaluated in studies with bevacizumab in cancer patient populations. A sensitive and specific immunoassay for detecting ADA in human serum was used to analyze the ADA samples (blood samples for assessment of ADA collected at specified timepoints).

Outcome measures

Outcome measures
Measure	PF-06439535 (CN) n=4 Participants Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21 day cycles.	Bevacizumab (EU) n=4 Participants Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.
Number of Participants With Anti-Drug Antibodies (ADA) Cycle 1_Day 1_ADA Positive	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Cycle 5_Day 1_ADA Positive	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) End of Treatment Positive	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 1 Cycle = 21 Days

Population: All participants who were randomized and received at least one dose of investigational product were used for ADA and NAb analyses. NAb were not tested thus no data were reported. Only samples that were determined positive for ADA would be further characterized for NAb.

Blood samples for assessment of ADA and NAb were collected at specified time point. Samples that were determined positive for ADA were further characterized for NAb using a single validated NAb assay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1 and Cycle 5, and before the last administration of the investigational product (up to Cycle 14 Day 1); 2.5 hours after initiation of bevacizumab infusion on Day 1 of Cycle 1 and Cycle 5; 1 Cycle = 21 Days

Population: Participants who were randomized and had at least 1 post dose drug concentration measurement, and had no major protocol deviations which influenced the pharmacokinetic (PK) assessment were included in the PK analysis. Data for analyzing endpoint were not collected.

The drug concentrations were determined using serum samples collected at the time points specified.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 9 Day 1 up to End of Treatment (up to Cycle 14 Day 21); 1 Cycle = 21 Days

Population: The safety population was defined as all participants who were randomized and received at least one dose of investigational product. To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.

Treatment emergent adverse event (TEAE) was defined as any adverse event that occurs after the beginning of the investigational product or any pre-existing adverse event that worsens after the beginning of the investigational product. Serious adverse events were assessed by the investigator. Severity of AE was graded based on NCI CTCAE version 4.03: Grade 3-SEVERE AE; Grade 4-LIFE-THREATENING consequences; urgent intervention indicated; Grade 5-DEATH RELATED TO AE.

Outcome measures

Outcome measures
Measure	PF-06439535 (CN) n=3 Participants Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21 day cycles.	Bevacizumab (EU) Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21 day cycles.
Number of Participants With TEAEs in Extension Period Participants with all causality AEs	3 Participants	—
Number of Participants With TEAEs in Extension Period Participants with all causality SAEs	1 Participants	—
Number of Participants With TEAEs in Extension Period Participants with all causality AEs of maximum grade 3 or 4	1 Participants	—
Number of Participants With TEAEs in Extension Period Participants with all causality AEs of maximum grade 5	0 Participants	—
Number of Participants With TEAEs in Extension Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs	2 Participants	—
Number of Participants With TEAEs in Extension Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related SAEs	0 Participants	—
Number of Participants With TEAEs in Extension Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs of maximum grade 3 or 4	1 Participants	—
Number of Participants With TEAEs in Extension Period Participants with PF-06439535 (CN) or bevacizumab (EU)-related AEs of maximum grade 5	0 Participants	—

Adverse Events

Treatment Period: PF-06439535 (CN)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Treatment Period: Bevacizumab (EU)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Extension Period: PF-06439535 (CN) or Bevacizumab (EU) > PF-06439535 (CN)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Period: PF-06439535 (CN) n=4 participants at risk Participants received PF-06439535 (CN) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21-day cycles.	Treatment Period: Bevacizumab (EU) n=4 participants at risk Participants received bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\^2) and carboplatin (starting dose of AUC 5 \[max=750 mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and bevacizumab (EU) were administered via IV infusion in order on 21-day cycles.	Extension Period: PF-06439535 (CN) or Bevacizumab (EU) > PF-06439535 (CN) n=3 participants at risk Participants in extension period who received PF-06439535 (CN) or bevacizumab (EU) (starting dose of 15 mg/kg) plus paclitaxel (starting dose of 175 mg/m\*2) and carboplatin (starting dose of AUC 5 \[max=750mg\]) for up to but not including 25 weeks as treatment period, followed by PF-06439535 (CN) monotherapy up to 2 years from randomization as extension period. Paclitaxel, carboplatin and PF-06439535 (CN) were administered via IV infusion in order on 21-day cycles.
Blood and lymphatic system disorders Neutropenia	25.0% 1/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	50.0% 2/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	0.00% 0/3 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.
General disorders Pyrexia	0.00% 0/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	25.0% 1/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	0.00% 0/3 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.
Infections and infestations Pneumonia	25.0% 1/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	0.00% 0/4 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.	33.3% 1/3 • From ICD through and up to 28 days after last dose of investigational product or prior to the start of new anticancer therapy, whichever occurred first (up to 311 days). To avoid risk re-identification of participants, data for extension period were reported in 1 arm as a total.

Other adverse events

Additional Information

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Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER