This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well PF-08634404 works when given alone or with chemotherapy . Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. The study is for adults with Transformed Small Cell Lung Cancer (T-SCLC ). T SCLC is a rare lung cancer that happens when one type of lung cancer changes into a more aggressive type after treatment stops working.
To join the study, participants must meet the following conditions:
* Are aged 18 years or older * Diagnosed with T-SCLC and have not received treatment for this type of lung cancer (a single cycle of chemotherapy may be permitted) * Prior diagnosis of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with tyrosine kinase inhibitors (TKIs) * Have healthy organs based on medical tests and are in good physical condition
After joining the study, adults will be given chemotherapy in addition to the study medicine. After this combination treatment is finished, the study medicine will be continued alone. Adults will receive the treatment through IV infusions (medicine given directly into a vein). All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.
Male or female participants aged ≥18 years at the time of informed consent.
Histologically or cytologically confirmed T-SCLC. Participant must have had a prior diagnosis of NSCLC with EGFR mutation which transformed to SCLC following the treatment with TKI(s).
Participants have not received systemic therapy for T-SCLC.
Have at least one measurable lesion as the target lesion based on RECIST v1.1.
Active or untreated CNS disease, including brain, brainstem, spinal cord, or meningeal metastases. Participants with definitively treated, clinically stable brain metastases may be eligible per protocol criteria. Participants with untreated asymptomatic brain metastases of longest diameter <1 cm are permitted if all of the following criteria are met: absence of neurological symptoms, no need for corticosteroids, and brain metastasis has no evidence of edema or hemorrhagic features.
Leptomeningeal disease
Clinically significant risk of hemorrhage or fistula, including tumor necrosis/cavitation, invasion or compression of major blood vessels, airways, or critical organs, or risk of tracheoesophageal or pleuroesophageal fistula
History of another malignancy (other than NSCLC) within 3 years prior to first dose, except for malignancies with negligible risk of metastasis or death (eg, adequately treated carcinoma in situ, nonmelanoma skin cancer)
Single group
PF-08634404
DrugConcentrate for solution for infusion
Chemotherapy
DrugInjection for intravenous use
Confirmed Objective Response Rate (ORR) as assessed by investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response. ORR using RECIST v1.1 as assessed by investigator.
Number of Participants with Adverse Events (AEs)
Adverse Events (AEs) as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
Duration of Response (DOR) as assessed by investigator based on RECIST v1.1
DOR is defined as the time from the first documentation of objective response (CR or PR) to the date of first documentation of disease progression (PD) or death due to any cause.
Progression Free Survival (PFS) as assessed by investigator based on RECIST v1.1
PFS is defined as the time from the date of randomization to the date of first documented disease progression, per RECIST v1.1, or death to any cause, whichever occurs first
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause. OS is secondary outcome measure in Phase 2 portion of the study.
Number of participants with Laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.