A Study to Learn About the Study Medicine Called PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)

Brief Summary
The purpose of this study is to understand if PF-08046054 alone works well compared to standard-of-care docetaxel alone in participants with non-small cell lung cancer (NSCLC) with PD-L1 expression greater than or equal to 1% and had cancer progression during or after treatment with PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted treatment regimen(s) for participants with known actionable genomic alterations (AGAs). Participants in this study must have cancer that has spread through their body or can't be removed with surgery or treated with definitive radiation.

Participants will randomly (like a flip of the coin) be assigned to either the PF-08046054 treatment group or the docetaxel treatment group. Participants in the PF-08046054 treatment group will receive an IV infusion (injected directly into the veins) twice during each 21-day cycle. Participants in the docetaxel treatment group will receive an IV infusion once during each 21-day cycle. Study participation may be up to 5 years if the participant's NSCLC is responding to treatment. The study team will see how each participant is doing with the study treatment during regular visits at the clinic.
Brief Title
A Study to Learn About the Study Medicine Called PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-Treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-800-718-1021
Central Contact Email
ClinicalTrials.gov_Inquiries@pfizer.com
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Carcinoma
Non-Small Cell Lung Cancer Metastatic
Non-Small Cell Lung Carcinoma
Eligibility Criteria
Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
* PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263.
* Participants who have NSCLC with known AGAs are permitted.
* Able to provide any of the following tumor tissues for biomarker analysis:

* Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or
* De novo biopsy from a tumor lesion, if medically feasible.
* Participants must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy, or have been intolerant to their most recent therapy:

Participants with no known AGAs must fulfill 1 of the following conditions:

* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, and unless contraindicated, a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
* Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment.

Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions:

* Must have received at least 1 relevant AGA-targeted therapy if locally available and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant
* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting.
* May have received PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).

Exclusion Criteria

* History of another malignancy within 3 years before the first dose of PF-08046054, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival \[OS\] ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
* Any central nervous system (CNS) lesions, unless definitively treated with CNS-directed local therapy (surgery and/or radiotherapy). Participants with definitively treated brain metastases are eligible if they meet the following criteria:

* The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least \>14 days prior to randomization (if requiring steroid treatment).
* No clinical or radiographic progression in the CNS following CNS-directed definitive radiotherapy and/or surgery.
* Time since CNS-directed treatment is ≥28 days prior to randomization.
* Participants with a history of leptomeningeal metastasis are excluded.
* Prior treatment with an anti-PD-L1 agent (where indicated per protocol) within 5 half-lives.
* Previous receipt of an MMAE-containing agent or prior docetaxel.

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participations are met.
Inclusion Criteria
Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
* PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263.
* Participants who have NSCLC with known AGAs are permitted.
* Able to provide any of the following tumor tissues for biomarker analysis:

* Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or
* De novo biopsy from a tumor lesion, if medically feasible.
* Participants must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy, or have been intolerant to their most recent therapy:

Participants with no known AGAs must fulfill 1 of the following conditions:

* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, and unless contraindicated, a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
* Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment.

Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions:

* Must have received at least 1 relevant AGA-targeted therapy if locally available and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant
* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting.
* May have received PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).

inclusion and
Gender
All
Gender Based
false
Keywords
Non-small cell lung cancer NSCLC
NSCLC
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07144280
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
C5851005
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
PADL1NK-005: A Randomized, Phase 3, Open-Label Study to Evaluate PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-Treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)
Primary Outcomes
Outcome Description
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
Outcome Measure
Overall Survival
Outcome Time Frame
Approximately 5 years
Secondary Ids
Secondary Id
2025-521281-97-00
Secondary Outcomes
Outcome Description
Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by BICR per RECIST v1.1, or death due to any cause, whichever occurs first.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
Outcome Description
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Objective Response Rate as assessed by BICR
Outcome Description
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Progression Free Survival as assessed by Investigator
Outcome Description
The proportion of participants who have a confirmed CR or PR, as best overall response assessed by investigator as per RECIST 1.1.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Objective Response Rate (ORR) as assessed by Investigator
Outcome Description
The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Duration of Response as assessed by BICR
Outcome Description
The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Duration of Response as assessed by Investigator
Outcome Description
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Outcome Time Frame
Through 90 days after the last study intervention; Approximately 5 years
Outcome Measure
Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation
Outcome Description
The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Mean scores and Change from baseline in the global health status/quality of life (QoL) score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Outcome Description
The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Mean scores and Change from baseline in physical functioning and role functioning scores on the EORTC QLQ-C30
Outcome Description
The EORTC QLQ-LC13 is a lung cancer specific module and consists of 13 item questionnaire assessing lung cancer-associated symptoms and treatment-related effects.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Mean scores and Change from Baseline in dyspnea, cough, and chest pain scores on the EORTC Quality of Life Cancer Questionnaire - Lung Cancer 13 QLQ-LC13
Outcome Description
TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to definitive deterioration (TTdD) in in the global health status/QoL score on the EORTC QLQ-C30
Outcome Description
TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.
Outcome Time Frame
Approximately 5 years
Outcome Measure
TTdD in physical functioning and role functioning scores on the EORTC QLQ-C30
Outcome Description
TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.
Outcome Time Frame
Approximately 5 years
Outcome Measure
TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13
Outcome Description
To characterize the pharmacokinetics (PK) of PF-08046054
Outcome Time Frame
Approximately 48 weeks
Outcome Measure
Pharmacokinetics (PK): Plasma concentration of PF-08046054 and and its components
Outcome Description
To characterize the immunogenicity of PF-08046054
Outcome Time Frame
Approximately 48 weeks
Outcome Measure
Incidence of Anti-Drug Antibody (ADA)
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES