Sasanlimab (PF-06801591, PD-1 Inhibitor) in Participants With Advanced Malignancies

• Sponsor: Pfizer (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04181788
• Collaborator: (none)
• Enrollment: 155
• Locations: 53
• Arms: 4
• Anticipated Duration (Months): 58
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 1b/2 protocol to evaluate pharmacokinetics, safety, efficacy, and pharmacodynamics of PF-06801591, a programmed death-1(PD-1) antagonist monoclonal antibody (mAb) in participants with advanced malignancies.

This study consists of 2 parts:

Phase 1b part (dose escalation and dose expansion) in patients with advanced malignancies in Asia and a global Phase 2 part in non small cell lung cancer (NSCLC) patients.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancies; Non-small-cell Lung Cancer	Drug: PF-06801591	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Open-Label Study to Evaluate Pharmacokinetics, Safety, Efficacy, and Pharmacodynamics of PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies
• Actual Study Start Date: Mar 18, 2020
• Actual Primary Completion Date: Mar 3, 2022
• Anticipated Study Completion Date: Jan 17, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A1 (Phase 1b)	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.
Experimental: Arm B1 (Phase 1b)	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.
Experimental: Arm A2 (Phase 2)	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.
Experimental: Arm B2 (Phase 2)	Drug: PF-06801591; A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.

Outcome Measures

Primary Outcome Measures

1. Phase 1b: Number of participants with Dose-Limiting Toxicities (DLT) [At the end of cycle 1 (28 days) for Arm A1 and (42 days) for Arm B1]

   A DLT is any of a predefined set of unacceptable adverse events that are observed and that are related to the investigational agent.

2. Phase 2: AUCτ of PF-06801591 at steady state, at Week 12 [Arm A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arm B2 (each cycle/ 42 days): Day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)]

   AUCτ is defined as area under the concentration-time curve during the dosing interval (τ).

3. Phase 2: Ctrough of PF-06801591 at steady state, at Week 12 [Arm A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arm B2 (each cycle/ 42 days): Day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)]

   Ctrough is defined as the concentration at the end of PF-06801591 dosing interval.

Secondary Outcome Measures

1. Number of participants with Treatment-Emergent Adverse Events [Baseline and up to 90 days post treatment period]

   Assessment of the overall safety and tolerability.

2. Number of participants with laboratory abnormalities [Baseline and up to 30 days post treatment period]

   Assessment of the overall safety and tolerability.

3. Pharmacokinetic parameters: AUC after first dose [Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)]

   AUC is defined as the area under the curve after the first dose.

4. Pharmacokinetic parameters: Ctrough after first dose [Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)]

   Ctrough after first dose is defined as the concentration at the end of the first dosing interval of PF-06801591.

5. Pharmacokinetic parameters: Ctrough at steady State [Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)]

   Ctrough at steady state is defined as the concentration at the end of PF-06801591 dosage interval at steady state.

6. Anti-Drug Antibody (ADA) levels of PF-06801591/Neutralizing antibodies titers for PF-06801591 [Arm A1 and Arm A2 (each cycle is 28 days): On day 1 of cycles 1, 2, 3, 4, 6, 8, 10 and EOT (up to 24 months). Arm B1 and Arm B2 (each cycle is 42 days): On day 1 of cycles 1, 2, 3, 4, 5, 7 and EOT (up to 24 months)]

   Immunogenicity assessment of PF-06801591.

7. Number of participants with Objective Response [Every 12 weeks (up to 24 months)]

   Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of first dose of study treatment (Phase 1b) or randomization (Phase 2) until the date of the first documentation of progression of disease.

8. Time to Response (TTR) [Every 12 weeks (up to 24 months)]

   TTR is the time from first dose of study treatment (Phase 1b) or randomization (Phase 2) to the date of first documentation of objective tumor response (CR or PR) by RECIST 1.1 that is subsequently confirmed.

9. PD-L1 expression in baseline [Baseline]

   Correlation(s) between PD-L1 expression in baseline tumor tissue and pharmacodynamic markers and/or clinical activity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years (≥ 20 years in Japan; ≥ 19 years in South Korea)

• Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate bone marrow function, renal and liver functions Phase 1b

• Histological or Cytological diagnosis of advanced solid tumor with clinical evidence of response to anti-PD-1 or PD-L1 agent

• Participant must have received at least 1 prior line of therapy for recurrent or metastatic disease, and must have progressed/relapsed, be refractory, or intolerant to standard therapy approved for the specific tumor type Phase 2

• Participants must have a documented diagnosis of stage III where participants are not candidates for surgical resection or definitive chemoradiation, or stage IV NSCLC

• EGFR mutation, BRAF mutation, and ALK or ROS1 translocation/rearrangement are not permitted

• Participants whose tumor is known to be PD-L1 positive (Tumor Proportion Score [TPS] ≥1%) or unknown are eligible

• Up to 1 line of prior therapy in advanced or metastatic disease settings allowed

• Participant should not have received prior treatment with anti PD-1/PD-L1 drugs

• At least one measurable lesion as defined by RECIST version 1.1

Exclusion Criteria:

• Participants with known symptomatic brain metastases requiring steroids

• Participants with Interstitial Lung Disease history or complication

• Q-T interval corrected for heart rate QTc > 450 msec for male participants or QTc > 470 msec for female participants or QTc > 480 msec in participants with right bundle branch block.

• Hypertension that cannot be controlled by medications (eg, systolic > 150 mmHg and diastolic > 90 mmHg) despite optimal medical therapy.

• Known or suspected hypersensitivity to active ingredient or excipients of the study drug.

• History of Grade ≥3 immune mediated AE (including AST/ ALT elevations that where considered drug related and cytokine release syndrome [CRS]) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy (For Phase 1b only).

• Vaccination with live attenuated vaccines within 4 weeks prior to randomization is prohibited; however inactivated vaccines are permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer hospital	Beijing	Beijing	China	100142
2	Chongqing Cancer Hospital	Chongqing	Chongqing	China	400030
3	Nanjing Drum Tower Hospital	Nanjing	Jiangsu	China	210008
4	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai	China	201107
5	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
6	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
7	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21656
8	Severance Hospital, Yonsei Univ. Health System	Seoul		Korea, Republic of	03722
9	Asan Medical Center	Seoul		Korea, Republic of	05505
10	Russian Research Centre for Radiology and Surgical Technologies	Saint Petersburg	Pesochny	Russian Federation	197758
11	Private medical institution "Euromedservice"	Pushkin	Saint-petersburg	Russian Federation	196603
12	Klinika UZI 4D, LLC	Pyatigorsk	Stavropol Region	Russian Federation	357502
13	State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital"	Yaroslavl	Yaroslavskaya Oblast'	Russian Federation	150054
14	Evimed Llc	Chelyabinsk		Russian Federation	454048
15	NUZ "Railway Clinical Hospital at the station Chelyabinsk of JSC "Russian Railways"	Chelyabinsk		Russian Federation	454048
16	Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine	Chelyabinsk		Russian Federation	454087
17	State Budgetary Healthcare Institution Chelyabinsk Regional Clinical Hospital	Chelyabinsk		Russian Federation	454092
18	Ars Medika Center, LLC	Kaliningrad		Russian Federation	236006
19	GBUZ Regional Clinical Hospital of Kaliningrad region	Kaliningrad		Russian Federation
20	Enlimed Llc	Kopeysk		Russian Federation	456620
21	Orenburg Regional Clinical Oncological Dispensary	Orenburg		Russian Federation	460021
22	Russian Scientific Center For Radiology and Surgical Technologies	Pesochny, Saint Petersburg		Russian Federation	197758
23	NS HI "Road Clinical Hospital of JSC "Russian Railways""	Saint Petersburg		Russian Federation	195271
24	LLC "Diagnostic center "Energo"	Saint Petersburg		Russian Federation	196247
25	LLC Medical Center "Magnit"	Saint-Petersburg		Russian Federation	19005
26	Llc "Mss"	Saint-Petersburg		Russian Federation	191025
27	North-West Medical Center	Saint-Petersburg		Russian Federation	191119
28	Road clinical clinic of JSC "RZD"	Saint-Petersburg		Russian Federation	192007
29	Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg	Saint-Petersburg		Russian Federation	195271
30	Medical University REAVIZ	Samara		Russian Federation	443001
31	Medical University REAVIZ	Samara		Russian Federation	443011
32	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
33	Taipei Veterans General Hospital	Taipei		Taiwan	11217
34	Limited Liability Company "MedX-ray International Group"	Pliuty Village, Obuhiv District	KIEV Region	Ukraine
35	Asklepion Medical Center	Khodosivka	Kyivska Oblast	Ukraine	08173
36	Municipal non-profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Dispensary	Sumy	Sumska Oblast	Ukraine	40022
37	"Medeya Sumy" LLC	Sumy	SUMY Region	Ukraine	40021
38	Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council	Dnipro		Ukraine	49102
39	LLC "AR DI PI Ukraine"	Dnipro		Ukraine	49102
40	Llc "Mdc Expert"	Dnipro		Ukraine	49102
41	PRECARPATHIAN NUCLEAR MEDICINE CENTER, Limited Liability Company	Ivano-Frankivsk		Ukraine	76011
42	Municipal Non-profit Enterprise "SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC	Ivano-Frankivsk		Ukraine	76018
43	Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center	Kropyvnytskyi		Ukraine	25006
44	Medical centre "Verum" Limited Liability Company	Kyiv		Ukraine	03039
45	Vita Сom LLC	Kyiv		Ukraine	03141
46	SI "Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine"	Kyiv		Ukraine	04050
47	The State Institution "Romodanov Neurosurgery Institute,	Kyiv		Ukraine	04050
48	Llc Medical Centre	Odesa		Ukraine	65006
49	Municipal Non-profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council	Odesa		Ukraine	65025
50	Llc Lidermed	Odesa		Ukraine	65062
51	Llc Medical Center Diamed	Uzhgorod		Ukraine	88000
52	Municipal nonprofit enterprise Central City Clinical Hospital of Uzhhorod City Council	Uzhgorod		Ukraine	8800
53	Мunicipal non-profit enterprise "Zhytomyr Regional Oncology Dispensary" of Zhytomyr Regional Co	Zhytomyr		Ukraine	10002

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04181788
• Other Study ID Numbers: B8011007; 2019-003818-14
• First Posted: Nov 29, 2019
• Last Update Posted: Jun 14, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Pfizer: Advanced solid tumors; NSCLC
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Jun 14, 2022