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Study of PF-07265807 in Participants With Metastatic Solid Tumors.

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ClinicalTrials.gov Identifier: NCT04458259
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

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
Neoplasm Metastasis Drug: PF-07265807 Drug: Sasanlimab Drug: Axitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 155 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation and expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE-FINDING, PHARMACOKINETIC, SAFETY AND TOLERABILITY STUDY OF PF 07265807 IN PARTICIPANTS WITH SELECTED ADVANCED OR METASTATIC SOLID TUMOR MALIGNANCIES
Actual Study Start Date : September 24, 2020
Estimated Primary Completion Date : December 25, 2023
Estimated Study Completion Date : December 25, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Axitinib

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 Name: ARRY-067

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 Name: ARRY-067

Drug: Sasanlimab
Given SC 225 mg Q3W
Other Name: PF-06801591; RN-888

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 Name: ARRY-067

Drug: Sasanlimab
Given SC 225 mg Q3W
Other Name: PF-06801591; RN-888

Drug: Axitinib
Dosed per package label starting with 5 mg PO BID
Other Name: AG-013736; Inlyta

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 Name: ARRY-067

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 Name: ARRY-067

Drug: Sasanlimab
Given SC 225 mg Q3W
Other Name: PF-06801591; RN-888

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 Name: ARRY-067

Drug: Sasanlimab
Given SC 225 mg Q3W
Other Name: PF-06801591; RN-888

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 Name: ARRY-067

Drug: Sasanlimab
Given SC 225 mg Q3W
Other Name: PF-06801591; RN-888

Drug: Axitinib
Dosed per package label starting with 5 mg PO BID
Other Name: AG-013736; Inlyta




Primary Outcome Measures :
  1. Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 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)

  2. Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs) [ Time Frame: Baseline through approximately 2 years ]
    AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

  3. Parts 1, 2, and 3: Number of participants with laboratory abnormalities [ Time Frame: Baseline through approximately 2 years ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing.

  4. Part 4: Overall Response Rate (ORR) [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluable via radiographical tumor assessment by RECIST v1.1

  5. Part 4: Complete Response (CR) [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluated via radiographical tumor assessment by RECIST v1.1


Secondary Outcome Measures :
  1. Parts 1, 2, and 3: Maximum plasma concentration (Cmax) and dose normalized (Cmax(dn)) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (Cmax / Cmax(dn)) and multiple dose (assuming steady state is achieved; Cmax,ss / Cmax,ss(dn)) pharmacokinetic (PK) parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  2. Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  3. Parts 1, 2, and 3: Minimum plasma concentration (Cmin) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (Cmin) and multiple dose (assuming steady state is achieved; Cmin,ss) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  4. Parts 1, 2, and 3: Average observed concentration (Cavg) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (Cavg) and multiple dose (assuming steady state is achieved; Cavg,ss) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  5. Parts 1, 2, and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) and dose normalized (AUClast(dn)) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (AUClast and AUClast(dn)) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  6. Parts 1, 2, and 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) and dose normalized (AUCtau(dn)) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Multiple dose assuming steady state is achieved (AUCtau,ss and AUCtau,ss(dn)) and single dose (as data permits; AUCtau) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  7. Parts 1, 2, and 3: Terminal elimination half-life (t1/2) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    As data permits, single dose (t1/2) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  8. Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) and dose normalized (AUCinf(dn)) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    As data permits, single dose (AUCinf and AUCinf(dn)) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  9. Parts 1, 2, and 3: Apparent oral clearance (CL/F) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    Single dose (CL/F) and multiple dose (as data permits) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  10. Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    As data permits, single dose (Vz/F) and multiple dose (Vss/F) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  11. Parts 1, 2, and 3: Accumulation ratio area under the curve (Rac,auc) and of maximum observed concentration (Rac,cmax) [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 hours post dose; Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14, predose and 2 hours post dose; Cycles 3-6 Days 1 and 14 predose ]
    As data permits, multiple dose (Rac,auc and Rac,cmax) pharmacokinetic parameters of PF-07265807, its metabolite, sasanlimab, or axitinib

  12. Parts 1, 2, and 3: ORR [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluable via radiographical tumor assessment by RECIST v1.1

  13. Part 4: Number of participants with treatment emergent AEs [ Time Frame: Baseline through approximately 2 years ]
    AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

  14. Part 4: Number of participants with laboratory abnormalities [ Time Frame: Baseline through approximately 2 years ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing

  15. Part4: PF-07265807 and its metabolite Pharmacokinetic (PK) concentration [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 2, and 4 hours post dose. Day 7 predose and 2 hours post dose; Cycles 2-6 Days 1 and 14: predose ]
    PK concentrations of PF-07265807 and its metabolite: Predose/trough concentration (Ctrough)

  16. Part4: PF-07265807 and its metabolite PK concentration [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 2, and 4 hours post dose. Day 7 predose and 2 hours post dose; Cycles 2-6 Days 1 and 14: predose ]
    PK concentrations of PF-07265807 and its metabolite: Post dose concentration (Cmax)

  17. Part 4, Cohorts 2-4: Sasanlimab PK concentration [ Time Frame: Each cycle is 21 days. Cycle 1 Days 1, 7, and 14: predose; Cycles 2-6 Day 1: predose. ]
    PK concentrations of sasanlimab: predose/trough concentration (Ctrough)

  18. Part 4, Cohort 4: Axitinib PK concentration [ Time Frame: Each cycle is 21 days. Cycle 1 Day 1: predose; Cycle 1 Day 14: predose, 2, and 4 hours post dose ]
    PK concentrations of axitinib: predose/trough concentration (Ctrough)

  19. Immunogenicity of sasanlimab when given in combination [ Time Frame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 6 Day 1 predose; Cycle 13 Day 1 predose; and then Day 1 every 6 cycles ]
    Incidence and titer of anti-sasanlimab ADA response

  20. Duration of Response [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluable via radiographical tumor assessment by RECIST v1.1

  21. Disease Control Rate [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluable via radiographical tumor assessment by RECIST v1.1

  22. Progression Free Survival [ Time Frame: Baseline through approximately 2 years ]
    Response will be evaluable via radiographical tumor assessment by RECIST v1.1



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

For Part 2, Part 3, and Part 4, Cohorts 2-4:

  • Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.
  • Discontinuation of prior checkpoint inhibitor for treatment-related toxicity.
  • Experienced >= G3 treatment-related irAE with prior PD-(L)1 agent.

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): NCT04458259


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, California
UCI Medical Center- Outpatient Pharmacy Recruiting
Orange, California, United States, 92868
UCI/Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Clinical & Translational Science Institute Not yet recruiting
San Francisco, California, United States, 94158
UCSF Helen Diller Family Comprehensive Cancer Center - Mission Hall Not yet recruiting
San Francisco, California, United States, 94158
UCSF Helen Diller Family Comprehensive Cancer Center Not yet recruiting
San Francisco, California, United States, 94158
UCSF Investigational Drugs Pharmacy Not yet recruiting
San Francisco, California, United States, 94158
United States, Colorado
Rocky Mountain Lions Eye Institute (RMLEI) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Duke Eye Center Recruiting
Durham, North Carolina, United States, 27705
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
United States, Texas
The University of Texas M. D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04458259    
Other Study ID Numbers: C4201002
ARRAY-067-102 ( Other Identifier: Alias Study Number )
2021-004270-59 ( EudraCT Number )
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: September 2021
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action