Advanced Cancer, Advanced Malignancies
Conditions
Keywords
Advanced Malignancies, Advanced Cancers, Advanced Cancer
Brief 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.
Interventions
DRUGPF-07994525
Oral administration
DRUGMidazolam
Oral administration
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, incidence and severity of participants with adverse events (AEs) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | 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) |
| Type, incidence and severity of participants with laboratory abnormalities | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Type, incidence, and severity (graded by NCI CTCAE version 5.0) of laboratory abnormalities |
| Number of participants with dose modifications | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Frequency of dose modifications (eg, dose delay, treatment interruptions, dose reductions, and treatment discontinuations) due to AEs |
| Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) | Baseline to end of DLT evaluation period | Occurrence of DLTs as defined by the protocol |
| Part 1: Recommended Monotherapy Dose for Expansion (RDE) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings |
| Part 2: Recommended Dose for future development | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Safety, and preliminary anti-tumor activity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single, Multiple Dose and food effect: Time to Maximum concentration (Tmax) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single, Multiple Dose and food effect: AUC from time zero to time of last measurable concentration (AUClast) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single Dose and food effect: Terminal Elimination half-life (t1/2) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single Dose and food effect: AUC versus time curve from time 0 extrapolated to infinity (AUCinf) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single, Multiple Dose and food effect: apparent clearance of drug (CL/F) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Single, Multiple Dose and food effect: Apparent volume of distribution during terminal phase (Vz/F) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Multiple Dose: AUC at steady state over the dosing interval (AUCtau) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Multiple Dose: Cmin as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Multiple Dose: Accumulation ratio (Rac) as data permit | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Pharmacokinetic (PK) assessments for PF-07994525 |
| Time to Maximum concentration (Tmax) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525 |
| AUC from time zero to time of last measurable concentration (AUClast) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525 |
| Maximum Observed Concentration (Cmax) | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | PK parameters of CYP3A4 probe substrate midazolam with and without PF-07994525 |
| 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) | — |
Countries
Canada, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed