Study of PF-07265807 in Participants With Metastatic Solid Tumors.
Study Details
Study Description
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
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Monotherapy Dose Escalation: Part 1 Monotherapy dose escalation of PF-07265807 in participants with select tumor types. |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
|
Experimental: Doublet Dose Escalation: Part 2 Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
Drug: Sasanlimab
Given SC 225 mg Q3W
Other Names:
|
Experimental: Triplet Dose Escalation: Part 3 Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with RCC. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label. |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
Drug: Sasanlimab
Given SC 225 mg Q3W
Other Names:
Drug: Axitinib
Dosed per package label starting with 5 mg PO BID
Other Names:
|
Experimental: Expansion Phase: Part 4, Cohort 1 PF-07265807 monotherapy in participants with METex14 mutant NSCLC. |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
|
Experimental: Expansion Phase: Part 4, Cohort 2 PF-07265807 with sasanlimab in participants with MSS CRC |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
Drug: Sasanlimab
Given SC 225 mg Q3W
Other Names:
|
Experimental: Expansion Phase: Part 4, Cohort 3 PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
Drug: Sasanlimab
Given SC 225 mg Q3W
Other Names:
|
Experimental: Expansion Phase: Part 4, Cohort 4 PF-07265807 with sasanlimab plus axitinib in participants with RCC |
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Names:
Drug: Sasanlimab
Given SC 225 mg Q3W
Other Names:
Drug: Axitinib
Dosed per package label starting with 5 mg PO BID
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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
- 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 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 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
Eligibility Criteria
Criteria
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.
For Part 2, Part 3, and Part 4, Cohorts 2-4:
- Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Henry Eye Clinic | Fayetteville | Arkansas | United States | 72703 |
2 | Highlands Oncology Group | Fayetteville | Arkansas | United States | 72703 |
3 | Highlands Oncology Group | Rogers | Arkansas | United States | 72758 |
4 | Highlands Oncology Group | Springdale | Arkansas | United States | 72762 |
5 | UCI Medical Center- Outpatient Pharmacy | Orange | California | United States | 92868 |
6 | UCI/Chao Family Comprehensive Cancer Center | Orange | California | United States | 92868 |
7 | Clinical & Translational Science Institute | San Francisco | California | United States | 94158 |
8 | UCSF Helen Diller Family Comprehensive Cancer Center - Mission Hall | San Francisco | California | United States | 94158 |
9 | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94158 |
10 | UCSF Investigational Drugs Pharmacy | San Francisco | California | United States | 94158 |
11 | Rocky Mountain Lions Eye Institute (RMLEI) | Aurora | Colorado | United States | 80045 |
12 | University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) | Aurora | Colorado | United States | 80045 |
13 | University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) | Aurora | Colorado | United States | 80045 |
14 | University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) | Aurora | Colorado | United States | 80045 |
15 | Community Health Network, Inc. | Indianapolis | Indiana | United States | 46219 |
16 | Community Health Network, Inc. | Indianapolis | Indiana | United States | 46227 |
17 | Community Health Network Cancer Center North | Indianapolis | Indiana | United States | 46250 |
18 | Community Health Network Investigational Drug Services | Indianapolis | Indiana | United States | 46250 |
19 | Community Health Network, Inc. | Indianapolis | Indiana | United States | 46250 |
20 | Community Health Network, Inc. | Indianapolis | Indiana | United States | 46256 |
21 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
22 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
23 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
24 | Duke Eye Center | Durham | North Carolina | United States | 27705 |
25 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
26 | The University of Texas M. D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
27 | Hamilton Health Sciences-Juravinski Cancer Centre | Hamilton | Ontario | Canada | L8V5C2 |
28 | University Health Network | Toronto | Ontario | Canada | M5G 2M9 |
29 | Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus | Quebec City | Quebec | Canada | G1J 1Z4 |
30 | CHU de Quebec-Universite Laval - Hotel Dieu de Quebec | Québec | Quebec | Canada | G1R 2J6 |
31 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
32 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 08035 | |
33 | Hospital Universitario Fundacion Jimenez Díaz | Madrid | Spain | 28040 | |
34 | Hospital Clinico Universitario de Valencia | Valencia | Spain | 46010 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C4201002
- ARRAY-067-102
- 2021-004270-59