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)

Plain English Summary

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) is a Phase 3 clinical trial sponsored by Pfizer studying Non-small Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Carcinoma. Tests if PF-08046054 works better than docetaxel for treating advanced lung cancer. For adults with PD-L1 positive non-small cell lung cancer who have tried other treatments. Participation involves IV infusions every 3 weeks for up to 5 years if the cancer responds. No other treatment options like surgery or radiation are available. The trial aims to enroll 680 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced lung cancer and PD-L1 expression ≥1% are eligible. Those with brain metastases or other cancers within the last 3 years are not. Must have tried at least one type of chemotherapy and a PD-(L)1 inhibitor. No prior treatment with similar drugs like docetaxel or MMAE-containing agents. This trial is studying Non-small Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures survival, helping patients understand how long they might live with treatment. The specific primary outcome measures are: Overall Survival (Approximately 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a gap in treatment options for advanced lung cancer patients. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-small Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Carcinoma, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high approval probability for this innovative treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 680 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have PD-L1 positive non-small cell lung cancer and have tried other treatments. Participation involves regular clinic visits and IV infusions every 3 weeks. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 680 participants

Interventions

• DRUG: PF-08046054 — Antibody Drug Conjugate Participants will receive PF-08046054, administered as an IV infusion.
• DRUG: Docetaxel monotherapy — Participants will receive Docetaxel, administered as an IV infusion.

Primary Outcomes

• Overall Survival (Approximately 5 years)

Secondary Outcomes

• Progression Free Survival (PFS) assessed by blinded independent central review (BICR) (Approximately 5 years)
• Objective Response Rate as assessed by BICR (Approximately 5 years)
• Progression Free Survival as assessed by Investigator (Approximately 5 years)
• Objective Response Rate (ORR) as assessed by Investigator (Approximately 5 years)
• Duration of Response as assessed by BICR (Approximately 5 years)

Full 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.

Trial Locations

• Alabama Oncology, Alabaster, Alabama, United States
• Alabama Oncology, Bessemer, Alabama, United States
• Alabama Oncology, Bruno Cancer Center, Birmingham, Alabama, United States
• Alabama Oncology, Birmingham, Alabama, United States
• Alabama Oncology, Birmingham, Alabama, United States
• Alabama Oncology, Birmingham, Alabama, United States
• Alabama Oncology, Birmingham, Alabama, United States
• Southern Cancer Center, Daphne, Alabama, United States
• Southern Cancer Center, PC, Foley, Alabama, United States
• Alaska Oncology and Hematology, Anchorage, Alaska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung cancer, metastatic lung cancer, non-small cell lung cancer, advanced lung cancer, PD-L1 positive lung cancer

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