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
Study of PF-07265807 in Participants With Metastatic Solid Tumors.
Kawai Norisuke
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Clinical Trials Information Desk
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Not Recruiting
Dec. 22, 2021
Dec. 22, 2021
155
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
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.
18age old over
No limit
Both
Solid Tumor
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Name: ARRY-067
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: 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
Drug: PF-07265807
Given QD 2 weeks on/1 week off
Other Name: ARRY-067
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: 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: 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
Pfizer Japan Inc.
National Cancer Center Hospital IRB
5-1-1, Tsukiji, Chuo-ku, Tokyo
+81-3-3542-2511
Chiken_CT@ml.res.ncc.go.jp
Approval
Nov. 10, 2021
No
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.
