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RecruitingInterventionalPhase 1

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

NCT ID: NCT07426757Sponsor: PfizerLast updated: 2026-06-01

Summary

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.

Arms & interventions

  • DrugPF-07994525

    Oral administration

  • DrugMidazolam

    Oral administration

Outcome measures

Primary

  • Type, incidence and severity of participants with adverse events (AEs)

    Type, incidence, severity (graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0), timing, seriousness, and relatedness of 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

    Type, incidence, and severity (graded by NCI CTCAE version 5.0) of 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

    Frequency of dose modifications (eg, dose delay, treatment interruptions, dose reductions, and treatment discontinuations) due to AEs

    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)

    Occurrence of DLTs as defined by the protocol

    Time frame: Baseline to end of DLT evaluation period

  • Part 1: Recommended Monotherapy Dose for Expansion (RDE)

    RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings

    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

    Safety, and preliminary anti-tumor activity

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Secondary

  • 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

  • Single, Multiple Dose and food effect: apparent clearance of drug (CL/F) as data permit

    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: Apparent volume of distribution during terminal phase (Vz/F) as data permit

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

  • Multiple Dose: AUC at steady state over the dosing interval (AUCtau) as data permit

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

  • Multiple Dose: Cmin as data permit

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

  • Multiple Dose: Accumulation ratio (Rac) as data permit

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

  • 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

  • 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

  • Maximum Observed Concentration (Cmax)

    Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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: 1. Serum M-protein \>0.5 g/dL by serum protein electrophoresis (SPEP) 2. Urinary M-protein excretion \>200 mg/24 hours by urine protein electrophoresis (UPEP) 3. 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).

Study locations (4)

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, 37203

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Tristar BMT

Nashville, Tennessee, 37203

Recruiting

TriStar Centennial Medical center

Nashville, Tennessee, 37203

Recruiting