Non-small Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Carcinoma
Conditions
Keywords
Non-small cell lung cancer NSCLC, 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.
Interventions
DRUGPF-08046054
Antibody Drug Conjugate Participants will receive PF-08046054, administered as an IV infusion.
DRUGDocetaxel monotherapy
Participants will receive Docetaxel, administered as an IV infusion.
Sponsors
Pfizer
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Approximately 5 years | Overall survival defined as the time from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) assessed by blinded independent central review (BICR) | Approximately 5 years | 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. |
| Objective Response Rate as assessed by BICR | Approximately 5 years | The proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1. |
| Progression Free Survival as assessed by Investigator | Approximately 5 years | 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. |
| Objective Response Rate (ORR) as assessed by Investigator | Approximately 5 years | The proportion of participants who have a confirmed CR or PR, as best overall response assessed by investigator as per RECIST 1.1. |
| Duration of Response as assessed by BICR | Approximately 5 years | 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. |
| Duration of Response as assessed by Investigator | Approximately 5 years | 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. |
| Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation | Through 90 days after the last study intervention; Approximately 5 years | 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. |
| 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) | Approximately 5 years | 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. |
| Mean scores and Change from baseline in physical functioning and role functioning scores on the EORTC QLQ-C30 | Approximately 5 years | 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. |
| 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 | Approximately 5 years | 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. |
| Time to definitive deterioration (TTdD) in in the global health status/QoL score on the EORTC QLQ-C30 | Approximately 5 years | TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery. |
| TTdD in physical functioning and role functioning scores on the EORTC QLQ-C30 | Approximately 5 years | TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery. |
| TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13 | Approximately 5 years | TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery. |
| Pharmacokinetics (PK): Plasma concentration of PF-08046054 and and its components | Approximately 48 weeks | To characterize the pharmacokinetics (PK) of PF-08046054 |
| Incidence of Anti-Drug Antibody (ADA) | Approximately 48 weeks | To characterize the immunogenicity of PF-08046054 |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed