An Open-Label Study to Evaluate PF-07994525 in Participants With Advanced Cancers

Official title

AN OPEN-LABEL PHASE 1 STUDY TO EVALUATE PF-07994525 IN PARTICIPANTS WITH ADVANCED MALIGNANCIES

Overview

This is an open-label, dose escalation and dose expansion study evaluating the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), and antitumor activity of PF-07994525 in participants with R/R MM. The study will consist of 2 parts: Part 1 (Dose Escalation) will consist of PF-07994525 dose escalation to assess the safety, tolerability, and preliminary antitumor activity in participants with R/R MM. In Part 2 (Dose expansion), PF-07994525 may be evaluated in additional participants with R/R MM to further assess safety, PK, PD, and preliminary anti-tumor activity.

Interventions

• Drug PF-07994525
  Oral administration
• Drug Midazolam
  Oral administration

Primary outcome measures

• Type, incidence and severity of participants with adverse events (AEs) [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Type, incidence and severity of participants with laboratory abnormalities [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Number of participants with dose modifications [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) [Time frame: Baseline to end of DLT evaluation period]
• Part 1: Recommended Monotherapy Dose for Expansion (RDE) [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Part 2: Recommended Dose for future development [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]

Secondary outcome measures (12)

• Objective response rate (ORR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator. [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Complete response rate (CRR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator. [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Time to response (TTR) per IMWG as determined by investigator [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Duration of response (DOR) per IMWG as determined by investigator [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Duration of complete response (DOCR) per IMWG as determined by investigator [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Progression-free survival (PFS) per IMWG as determined by investigator [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Overall survival (OS) [Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)]
• Single, Multiple Dose and food effect: Maximum Observed Concentration (Cmax) [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single, Multiple Dose and food effect: Time to Maximum concentration (Tmax) [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single, Multiple Dose and food effect: AUC from time zero to time of last measurable concentration (AUClast) [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single Dose and food effect: Terminal Elimination half-life (t1/2) as data permit [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]
• Single Dose and food effect: AUC versus time curve from time 0 extrapolated to infinity (AUCinf) as data permit [Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at the time of informed consent.
• Prior diagnosis of MM as defined according to IMWG criteria (Rajkumar et al. 2014)

Measurable disease based on IMWG criteria as defined by at least 1 of the following:

• Serum M-protein >0.5 g/dL by serum protein electrophoresis (SPEP)
• Urinary M-protein excretion >200 mg/24 hours by urine protein electrophoresis (UPEP)
• Serum immunoglobulin Free Light Chain (FLC) ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65)

• Participants must be refractory to, or intolerant to, all established therapies known to provide clinical benefit in multiple myeloma that are an appropriate therapeutic option, in the judgement of the investigator. A minimum of 3 prior lines of therapy are required.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Exclusion criteria

• Active plasma cell leukemia, Smoldering MM, Waldenströms macroglobulinemia, Amyloidosis, POEMS Syndrome.
• Autologous stem cell transplant within 12 weeks prior to enrollment or active Graft-versus-host disease (GVHD).
• Active or suspected cerebral/meningeal disease related to the underlying malignancy.
• Any active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), known HIV or AIDS related illness, unless deemed not clinically significant by the investigator (eg, onychomycosis).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center — Coral Gables
• Sylvester Comprehensive Cancer Center - Coral Springs — Coral Springs
• University of Miami Hospital and Clinics - Deerfield Beach — Deerfield Beach
• University of Miami Hospital and Clinics - Doral — Doral
• Sylvester Comprehensive Cancer Center - Hollywood — Hollywood
• Sylvester Comprehensive Cancer Center — Miami
• University of Miami Hospital and Clinics — Miami
• Sylvester Comprehensive Cancer Center- Kendall — Miami
• … and 9 more centers

Canada · 1 center

• Arthur J.E. Child Comprehensive Cancer Centre — Calgary

Identifiers

NCT: NCT07426757 · C6331001 · KAT2i

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗