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

Sponsor
Pfizer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04458259
Collaborator
(none)
161
34
7
40.9
4.7
0.1

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

Study Type:
Interventional
Anticipated Enrollment :
161 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Dose escalation and expansionDose 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 :
Sep 24, 2020
Anticipated Primary Completion Date :
Feb 22, 2024
Anticipated Study Completion Date :
Feb 22, 2024

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:
  • 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 Names:
  • ARRY-067
  • Drug: Sasanlimab
    Given SC 225 mg Q3W
    Other Names:
  • 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 Names:
  • ARRY-067
  • Drug: Sasanlimab
    Given SC 225 mg Q3W
    Other Names:
  • PF-06801591; RN-888
  • Drug: Axitinib
    Dosed per package label starting with 5 mg PO BID
    Other Names:
  • 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 Names:
  • 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 Names:
  • ARRY-067
  • Drug: Sasanlimab
    Given SC 225 mg Q3W
    Other Names:
  • 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 Names:
  • ARRY-067
  • Drug: Sasanlimab
    Given SC 225 mg Q3W
    Other Names:
  • 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 Names:
  • ARRY-067
  • Drug: Sasanlimab
    Given SC 225 mg Q3W
    Other Names:
  • PF-06801591; RN-888
  • Drug: Axitinib
    Dosed per package label starting with 5 mg PO BID
    Other Names:
  • AG-013736; Inlyta
  • Outcome Measures

    Primary Outcome Measures

    1. 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)

    2. 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

    3. 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.

    4. Part 4: Overall Response Rate (ORR) [Baseline through approximately 2 years]

      Response will be evaluable via radiographical tumor assessment by RECIST v1.1

    5. 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

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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

    8. 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

    9. 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

    10. 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

    11. 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

    12. 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

    13. 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

    14. 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

    15. 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

    16. 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

    17. 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

    18. 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

    19. Parts 1, 2, and 3: ORR [Baseline through approximately 2 years]

      Response will be evaluable via radiographical tumor assessment by RECIST v1.1

    20. 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

    21. Part 4: Number of participants with laboratory abnormalities [Baseline through approximately 2 years]

      Laboratory abnormalities as characterized by type, frequency, severity, and timing

    22. 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

    23. 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

    24. 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

    25. 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

    26. 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

    27. Duration of Response [Baseline through approximately 2 years]

      Response will be evaluable via radiographical tumor assessment by RECIST v1.1

    28. Disease Control Rate [Baseline through approximately 2 years]

      Response will be evaluable via radiographical tumor assessment by RECIST v1.1

    29. Progression Free Survival [Baseline through approximately 2 years]

      Response will be evaluable via radiographical tumor assessment by RECIST v1.1

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT04458259
    Other Study ID Numbers:
    • C4201002
    • ARRAY-067-102
    • 2021-004270-59
    First Posted:
    Jul 7, 2020
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022

    Study Results

    No Results Posted as of Aug 23, 2022