Advanced MalignanciesPhase 1NCT07426757
An Open-Label Study to Evaluate PF-07994525 in Participants With Advanced Cancers
A Phase 1 study testing PF-07994525 and Midazolam in people with Advanced Malignancies and Advanced Cancer, run by Pfizer at 26 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignancies, Advanced Cancer
- What is being tested?
- PF-07994525 and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 26 sitesin 2 countries
- Study dates
- 1 Jul 2026to 10 Jul 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
26 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
26 sites in 2 countries
United States24 sites, 24 recruiting
- Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, 30308
- Recruiting
Emory University Hospital
Atlanta, Georgia, 30322
- Recruiting
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
- Recruiting
Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center
Coral Gables, Florida, 33146
- Recruiting
Sylvester Comprehensive Cancer Center - Coral Springs
Coral Springs, Florida, 33065
- Recruiting
University of Miami Hospital and Clinics - Deerfield Beach
Deerfield Beach, Florida, 33442
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
- Recruiting
Presbyterian/St. Luke's Medical Center
Denver, Colorado, 80218
- Recruiting
Sylvester Comprehensive Cancer Center- Doral
Doral, Florida, 33166
- Recruiting
Sylvester Comprehensive Cancer Center - Hollywood
Hollywood, Florida, 33021
- Recruiting
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
- Recruiting
University of Miami Hospital and Clinics
Miami, Florida, 33136
- Recruiting
Sylvester Comprehensive Cancer Center- Kendall
Miami, Florida, 33176
- Recruiting
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
Smilow Cancer Hospital - Yale New Haven Health
New Haven, Connecticut, 06510
- Recruiting
Yale-New Haven Hospital-Yale Cancer Center
New Haven, Connecticut, 06510
- Recruiting
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, 06511
- Recruiting
Yale University - Smilow Cancer Hospital; C/O Thomas Ferencz, RPh, BCOP
New Haven, Connecticut, 06511
- Recruiting
Smilow Cancer Hospital - North Haven
North Haven, Connecticut, 06473
- Recruiting
Sylvester Comprehensive Cancer Center - Sole Mia
North Miami, Florida, 33181
- Recruiting
Sylvester Comprehensive Cancer Center - Plantation
Plantation, Florida, 33324
Canada2 sites, 2 recruiting
- Recruiting
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2
- Recruiting
University Health Network- Princess Margaret Cancer Centre
Toronto, Ontario, M5G2M9
About this study
Official title: 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.
- Conditions
- Advanced Malignancies, Advanced Cancer
- Being tested
- PF-07994525, Midazolam
- Keywords
- Advanced Malignancies, Advanced Cancers, Advanced Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-07994525Drug
Oral administration
MidazolamDrug
Oral administration
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Monotherapy Dose Expansion Receives: Drug: PF-07994525; Drug: Midazolam |
| Part 2 | Experimental | Monotherapy Dose Escalation Receives: Drug: PF-07994525 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From the first day through 30-37 days after the last study treatment, up to approximately 2 years
Secondary outcomes (20)
Objective response rate (ORR) per International Myeloma Working Group (IMWG) response criteria as determined by investigator.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)
Overall survival (OS)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From the first day through 30-37 days after the last study treatment, up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2026
- Study start1 Jul 2026
- Primary completion10 Jul 2029 (estimated)
- Study completion10 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced MalignanciesStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07426757
- Sponsor's protocol ID
- C6331001
- Other IDs
- KAT2i
- Status last verified
- Oct 2026
- First submitted
- 16 Feb 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.