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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Cancer; Advanced Malignancies
• Intervention / Treatment: Drug: Midazolam; Drug: PF-07994525

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Centennial Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute - Pharmacy
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tristar BMT
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Monotherapy Dose Escalation	Drug: Midazolam; Oral administration; Drug: PF-07994525; Oral administration
Experimental: Part 2; Monotherapy Dose Expansion	Drug: PF-07994525; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	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	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	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	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	From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator.		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.		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		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		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		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		Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)
Overall survival (OS)		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)	Pharmacokinetic (PK) assessments for PF-07994525	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)	Pharmacokinetic (PK) assessments for PF-07994525	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)	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	From the first day through 30-37 days after the last study treatment, up to approximately 2 years
Multiple Dose: Cmin as data permit	Pharmacokinetic (PK) assessments for PF-07994525	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	Pharmacokinetic (PK) assessments for PF-07994525	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)	PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525	From the first day through 30-37 days after the last study treatment, up to approximately 2 years
Time to Maximum concentration (Tmax)	PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525	From the first day through 30-37 days after the last study treatment, up to approximately 2 years
Maximum Observed Concentration (Cmax)	PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525	From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): July 10, 2029
• Study Completion (Estimated): July 10, 2030

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Cancer; Advanced Malignancies; Advanced Cancers
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Midazolam
• Other Study ID Numbers: C6331001; KAT2i (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No