A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
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| ClinicalTrials.gov Identifier: NCT05355701 |
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Recruitment Status :
Recruiting
First Posted : May 2, 2022
Last Update Posted : April 30, 2024
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
- Study Details
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Brief Summary:
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines (called binimetinib) in people with solid tumors.
This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer.
All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine:
- People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day.
- People with colorectal cancer may also receive cetuximab. Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV).
Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Melanoma Non-Small-Cell Lung Cancer Thyroid Cancer Glioma | Drug: PF-07799933 Drug: binimetinib Biological: cetuximab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 156 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS |
| Actual Study Start Date : | July 5, 2022 |
| Estimated Primary Completion Date : | July 29, 2027 |
| Estimated Study Completion Date : | January 29, 2029 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Cetuximab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Monotherapy dose escalation (Part 1)
Participants will receive PF-07799933
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Drug: PF-07799933
Tablet
Other Name: ARRY-440 |
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Experimental: Combination dose escalation (Part 2)
Participants will receive PF-07799933 in combination with binimetinib or cetuximab
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Drug: PF-07799933
Tablet
Other Name: ARRY-440 Drug: binimetinib Tablet
Other Name: Mektovi, PF-06811462, MEK162 Biological: cetuximab Injection for intravenous use
Other Name: Erbitux |
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Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1
Participants will receive PF-07799933
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Drug: PF-07799933
Tablet
Other Name: ARRY-440 |
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Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2
Participants will receive PF-07799933
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Drug: PF-07799933
Tablet
Other Name: ARRY-440 Drug: binimetinib Tablet
Other Name: Mektovi, PF-06811462, MEK162 |
Primary Outcome Measures :
- Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab
- Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) [ Time Frame: Baseline to 28 days after last dose of study medication ]AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
- Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) [ Time Frame: Baseline to 28 days after last dose of study treatment ]Laboratory abnormalities as characterized by type, frequency, severity, and timing
- Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2) [ Time Frame: Baseline to 28 days after last dose of study treatment ]Vital sign abnormalities as characterized by type, frequency, severity, and timing
- Dose interruptions due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]Incidence of dose interruptions due to AEs
- Dose dose modifications due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]Incidence of dose modifications due to AEs
- Discontinuations due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]Incidence of discontinuations due to AEs
- MTD (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]Maximum tolerated dose (MTD)
- RDE (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]Recommended dose for expansion (RDE)
- Overall response rate (ORR) (Part 3) [ Time Frame: Baseline to 2 years ]Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) [ Time Frame: Baseline to 28 days after last dose of study treatment ]Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Secondary Outcome Measures :
- Part 1 and Part 2: ORR [ Time Frame: Baseline to 2 years ]ORR as assessed using the RECIST version 1.1.
- Part 1/2/3: Intracranial response [ Time Frame: Baseline to 2 years ]Intracranial response by RECIST version 1.1 (for brain metastases) & Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).
- Part 1 and Part 2: Duration of response [ Time Frame: Baseline to 2 years ]Duration of response
- Part 3: Number of participants with treatment-emergent adverse events (AEs) [ Time Frame: Baseline to 2 years ]AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
- Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities [ Time Frame: Baseline to 2 years ]Laboratory abnormalities as characterized by type, frequency, severity, and timing
- Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities [ Time Frame: Baseline to 2 years ]Vital sign abnormalities as characterized by type, frequency, severity, and timing
- Part 3: Dose interruptions due to AEs [ Time Frame: Baseline to 2 years ]Incidence of dose interruptions due to AEs
- Part 3: Dose dose modifications due to AEs [ Time Frame: Baseline to 2 years ]Incidence of dose modifications due to AEs
- Part 3: Discontinuations due to AEs [ Time Frame: Baseline to 2 years ]Incidence of discontinuations due to AEs
- Part 3: Time to event endpoints in each combination [ Time Frame: Baseline to 2 years ]Time to event endpoints in each combination
- Part 3: Disease Control Rate (DCR) [ Time Frame: Baseline to 2 years ]DCR
- Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, Cmax
- Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, Tmax
- Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, AUClast
- Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, AUC24
- Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, AUC48
- Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, t½
- Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, AUCinf
- Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, CL/F
- Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Single dose, Vz/F
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Cmax
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Ctrough
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Tmax
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, AUCτ
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, CL/F
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Cav
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, PTR
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac) [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ)
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2 [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, t1/2
- Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F [ Time Frame: Baseline to 2 years ]PK parameters of PF-07799933, Multiple dose, Vz/F
- Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, Cmax
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, Tmax
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, AUClast
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, t½
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, AUCinf
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, CL/F
- Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F [ Time Frame: Baseline to 2 years ]PK parameters of CYP3A4 probe substrate midazolam, Vz/F
- Part 3: TTR [ Time Frame: Baseline to 2 years ]Time to response (TTR)
- Part 3: DOR [ Time Frame: Baseline to 2 years ]Duration of response (DOR)
- Part 3: PFS [ Time Frame: Baseline to 2 years ]Progression-free survival (PFS)
- Part 3: OS [ Time Frame: Baseline to 2 years ]Overall survival (OS)
- Number of participants with clinically significant physical exam abnormalities (Part 3) [ Time Frame: Baseline to 28 days after last dose of study medication ]Physical exam abnormalities as as graded by NCI CTCAE version 5.0
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
This study is seeking participants who meet the following eligibility criteria:
Inclusion Criteria:
- Diagnosis of advanced/metastatic solid tumor including primary brain tumor.
- Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid [DNA], or ctDNA).
- Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1 and Part 2).
- Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies
Exclusion Criteria:
- Brain metastasis larger than 4 cm
- Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
- For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05355701
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Locations
Show 43 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT05355701 |
| Other Study ID Numbers: |
C4761001 BRAF Class 2 ( Other Identifier: Alias Study Number ) |
| First Posted: | May 2, 2022 Key Record Dates |
| Last Update Posted: | April 30, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Thyroid Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Head and Neck Neoplasms |
Endocrine System Diseases Thyroid Diseases Cetuximab Antineoplastic Agents, Immunological Antineoplastic Agents |