Neoplasm Metastasis
Conditions
Keywords
TAMK (TAM kinase), MER (mer proto-oncogene), MERTK (mer proto-oncogene tyrosine kinase), AXL (AXL receptor tyrosine kinase), AXL/MER, Selective kinase inhibitor, PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death ligand 1), Immune modulator, Advanced Cancer, Metastatic Cancer, Solid Tumor Cancer, Metastatic Solid Tumor, Cervical Cancer, Gastric Cancer, Esophageal Cancer, Endometrial Cancer, Hepatocellular carcinoma (HCC), Melanoma, Merkel Cell Carcinoma, High levels of MicroSatellite Instability deficient MisMatch Repair (MSI-H-dMMR) tumor, Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC), Renal cell carcinoma (RCC), Urothelial carcinoma, Colorectal cancer (CRC)
Brief summary
A First-in-Human Pharmacokinetic, Safety, and Tolerability Study of PF-07265807 as Monotherapy and in Combination in Participants with Advanced or Metastatic Solid Tumors
Interventions
DRUGPF-07265807
Given 2 weeks on/1 week off
DRUGSasanlimab
Given SC Q3W
DRUGAxitinib
Dosed per package label starting with 5 mg PO BID
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation and expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least one measurable (Parts 1-4) or non-measurable lesion (Parts 1-3), not previously irradiated, as defined by RECIST 1.1 * ECOG Performance Status 0 or 1, 2 with approval * Adequate Bone Marrow Function * Adequate Renal Function * Adequate Liver Function * Resolved acute effects of any prior therapy * Able to provide adequate archival tumor tissue or freshly obtained tumor tissue (some participants will require mandatory pre- and on-treatment biopsy is part of the biomarker cohort). * Life expectancy of at least 3 months. * Part 1 and Part 2: Participants who are intolerant or resistant to standard treatment for selected solid tumors. * Part 3: Participants with advanced/metastatic RCC with a clear cell component and progressed with no standard therapy available. * Part 4, Cohort 1: Participants with NSCLC with METex14-skipping alteration(s) and progressed on at least 1 prior therapy. * Part 4, Cohort 2: Participants with MSS CRC with intermediate TMB and progressed with no satisfactory alternative treatment available, but has not received prior treatment with an anti-PD-(L)1 therapy. * Part 4, Cohort 3: Participants with metastatic gastric or GEJ adenocarcinoma that is PD-L1 positive that has progressed on at least 2 but no more than 3 prior chemotherapy regiments, but has not received prior treatment with an anti-PD-(L)1 therapy. * Part 4, Cohort 4: Participants with metastatic RCC with a clear cell component with IMDC intermediate or poor risk that have not received any prior systemic therapy for metastatic disease.
Exclusion criteria
* Known active uncontrolled or symptomatic CNS metastases. * Any other active malignancy within 2 years prior to enrollment. * Major surgery within 6 weeks, radiation therapy within 4 weeks, systemic anti-cancer therapy within 2 week or 5 half-lives (4 weeks or 5 half-lives for antibody therapies or investigational drug(s) taken on another study) prior to study entry. * Active or history of autoimmune disease requiring \>10mg/day prednisone or other concurrent immunosuppressive therapy. * Active, uncontrolled infection (controlled HBV, HCV, HIV/AIDS may be allowed) as defined in protocol. * Retinal or other serious ophthalmic disorders as defined in protocol. * Clinically significant cardiac disease as defined in protocol. * Uncontrolled HTN that cannot be controlled by medications. * Inability to consume or absorb study drug. * Known or suspected hypersensitivity to PF-07265807. * Prohibited concomitant medications as defined in protocol. * Active inflammatory GI disease, uncontrollable chronic diarrhea, or previous gastric resection or lap band surgery affecting absorption. * Active bleeding disorder. * Discontinuation of prior checkpoint inhibitor for treatment-related toxicity. * Experienced \>= G3 treatment-related irAE with prior PD-(L)1 agent. * Prior treatment with selective AXL/MERTK inhibitors For participants receiving sasanlimab: \- Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs) | Baseline through day 21 or 42 | DLTs will be evaluated during the first cycle (day 21) or two cycles (day 42). The number of DLTs will be used to determine the maximum tolerated dose (MTD) |
| Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs) | Baseline through approximately 2 years | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy |
| Parts 1, 2, and 3: Number of participants with laboratory abnormalities | Baseline through approximately 2 years | Laboratory abnormalities as characterized by type, frequency, severity, and timing. |
| Part 4: Overall Response Rate (ORR) | Baseline through approximately 2 years | Response will be evaluable via radiographical tumor assessment by RECIST v1.1 |
| Part 4, Cohort 4: Complete Response (CR) | Baseline through approximately 2 years | Response will be evaluated via radiographical tumor assessment by RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Time to reach maximum plasma concentration at steady state (Tmax,ss) of axitinib | Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose | Multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of axitinib |
| Parts 1, 2, and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | Single dose (AUClast) pharmacokinetic parameters of PF-07265807 and its metabolite |
| Parts 2 and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of sasanlimab | Through study completion, an average of 1 year | Single dose (AUClast) pharmacokinetic parameters of sasanlimab |
| Parts 1, 2, and 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of PF-07265807 and its metabolite |
| Part 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of axitinib | Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose | Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of axitinib |
| Parts 1, 2, and 3: Terminal elimination half-life (t1/2) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | As data permits, single dose (t1/2) pharmacokinetic parameters of PF-07265807 and its metabolite |
| Parts 2 and 3: Terminal elimination half-life (t1/2) of sasanlimab | Through study completion, an average of 1 year | As data permits, single dose (t1/2) pharmacokinetic parameters of sasanlimab |
| Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | As data permits, single dose (AUCinf) pharmacokinetic parameters of PF-07265807 and its metabolite |
| Parts 2 and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of sasanlimab | Through study completion, an average of 1 year | As data permits, single dose (AUCinf) pharmacokinetic parameters of sasanlimab |
| Parts 1, 2, and 3: Apparent oral clearance (CL/F) of PF-07265807 | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | As data permits, single dose (CL/F) and multiple dose pharmacokinetic parameters of PF-07265807 |
| Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab | Through study completion, an average of 1 year | As data permits, single dose (CL/F) pharmacokinetic parameters of sasanlimab |
| Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) of PF-07265807 | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | As data permits, single dose (Vz/F) and multiple dose (Vss/F) pharmacokinetic parameters of PF-07265807 |
| Parts 1, 2, and 3: Maximum plasma concentration (Cmax) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | Single dose (Cmax) and multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) parameters of PF-07265807 and its metabolite |
| Parts 1, 2, and 3: ORR | Baseline through approximately 2 years | Response will be evaluable via radiographical tumor assessment by RECIST v1.1 |
| Part 4: Number of participants with treatment emergent AEs | Baseline through approximately 2 years | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy |
| Part 4: Number of participants with laboratory abnormalities | Baseline through approximately 2 years | Laboratory abnormalities as characterized by type, frequency, severity, and timing |
| Part 4: Trough concentration (Ctrough) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose | Predose (Ctrough) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite |
| Part 4: Post dose concentration (Cmax) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose | Post dose (Cmax) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite |
| Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) of sasanlimab | Each cycle is 21 days. Cycle 1 Days 1, 7, and 14, Cycle 2 Day 1, Cycle 7 Day 1, and every 6 cycles thereafter predose | Predose (Ctrough) pharmacokinetic (PK) parameter of sasanlimab |
| Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib | Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose | Predose (Ctrough) pharmacokinetic (PK) parameter of axitinib |
| Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination | Through study completion, an average of 1 year | Incidence and titer of anti-sasanlimab ADA response |
| Duration of Response | Baseline through approximately 2 years | Response will be evaluable via radiographical tumor assessment by RECIST v1.1 |
| Disease Control Rate | Baseline through approximately 2 years | Response will be evaluable via radiographical tumor assessment by RECIST v1.1 |
| Progression Free Survival | Baseline through approximately 2 years | Response will be evaluable via radiographical tumor assessment by RECIST v1.1 |
| Parts 2 and 3: Apparent terminal volume of distribution (Vz/F) of sasanlimab | Through study completion, an average of 1 year | As data permits, single dose (Vz/F) pharmacokinetic parameters of sasanlimab |
| Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab | Through study completion, an average of 1 year | Single dose (Cmax) pharmacokinetic (PK) parameters of sasanlimab |
| Part 3: Maximum plasma concentration at steady state (Cmax,ss) of axitinib | Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose | Multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) parameters of axitinib |
| Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) of PF-07265807 and its metabolite | Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose | Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of PF-07265807 and its metabolite |
| Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab | Through study completion, an average of 1 year | Single dose (Tmax) pharmacokinetic parameters of sasanlimab |
Countries
Canada, Italy, Japan, Spain, United States
Outcome results
None listed