PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

• ClinicalTrials.gov Identifier: NCT03460977
• Recruitment Status: Recruiting
• First Posted: March 9, 2018
• Last Update Posted: February 24, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 12, 2018
• First Posted Date: March 9, 2018
• Last Update Posted Date: February 24, 2023
• Actual Study Start Date: April 17, 2018
• Estimated Primary Completion Date: September 18, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 23, 2022)

• Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [ Time Frame: Baseline up to 90 days ]
  First cycle DLTs will be utilized to determine the MTD
• Overall safety profile including adverse events [ Time Frame: Baseline up to approximately 2 years ]
  Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03])
• Preliminary efficacy determination as evaluated by disease specific response criteria [ Time Frame: Through study completion, approximately 2 years past last patient first visit. ]
  Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC.
• Overall safety profile including laboratory abnormalities [ Time Frame: Baseline up to approximately 2 years ]
  Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.
• Overall safety profile including vital signs [ Time Frame: Baseline up to approximately 2 years ]
  Vital sign changes from baseline including blood pressure, heart rate, ECG changes.

Original Primary Outcome Measures (submitted: March 2, 2018)

• Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [ Time Frame: Baseline up to 90 days ]
  First cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations. A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents.
• Overall safety profile including adverse events [ Time Frame: Baseline up to approximately 2 years ]
  Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any lab abnormalities. Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03]), timing, seriousness, and relationship to study therapy.
• Preliminary efficacy determination as evaluated by disease specific response criteria [ Time Frame: Through study completion, approximately 2 years past last patient first visit. ]
  Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC)
• Overall safety profile including laboratory abnormalities [ Time Frame: Baseline up to approximately 2 years ]
  Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.
• Overall safety profile including vital signs [ Time Frame: Baseline up to approximately 2 years ]
  Vital sign changes from baseline including blood pressure, heart rate, ECG changes.

Current Secondary Outcome Measures (submitted: September 23, 2022)

• Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type. [ Time Frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years. ]
  Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC)
• Evaluate overall survival [ Time Frame: Baseline up to approximately 2 years ]
  Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
• Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits
• Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits
• Pharmacokinetic Parameters: Area Under the Curve (AUC) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits
• Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits
• Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits
• Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [ Time Frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit ]
  Singe dose and multiple dose PK will be calculated as data permits
• Evaluate the impact of PF-06821497 on patient reported outcomes. [ Time Frame: At specific time-points from Cycle 1 Day 1 to End of Treatment visit. ]
  Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.

Original Secondary Outcome Measures (submitted: March 2, 2018)

• Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), and metastatic free survival (MFS) [ Time Frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years. ]
  Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC)
• Evaluate overall survival [ Time Frame: Baseline up to approximately 2 years ]
  Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
• Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits including Maximum Observed Plasma Concentration (Cmax).
• Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits including Time to Reach Maximum Observed Plasma Concentration (Tmax).
• Pharmacokinetic Parameters: Area Under the Curve (AUC) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits including Area Under the Cuvce (AUC).
• Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits including Apparent Oral Clearance (CL/F). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
• Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Single dose and multiple dose PK will be calculated as data permits including Apparent Volume of Distribution (Vz/F). Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
• Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit ]
  Singe dose and multiple dose PK will be calculated as data permits including Plasma Decay Half-Life (t1/2). Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
• Official Title: A Phase I Dose Escalation And Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL)
• Brief Summary: A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
• Detailed Description: This is an open label, multi center, Phase 1 dose escalation and dose expansion study of PF-06821497 administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. Part 1A will evaluate safety and target modulation of PF-06821497 monotherapy in patients with SCLC, FL and CRPC. PF-06821497 will be administered as monotherapy in patients with FL in Part 1B dose escalation and to patients with CRPC in Part 1C dose escalation. For Part 2A (dose escalation combination therapy), PF-06821497 will be administered in combination with SOC in patients with CRPC and SCLC. For Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or PF-06821497 in combination with SOC. Once safety and adequate target modulation has been established in Part 1A, Parts 1B and 2A of the trial will be initiated. Part 1C (monotherapy dose escalation) will determine the MTD of single agent PF-06821497 in patients with mCRPC. Japan and China monotherapy cohorts will evaluate the safety, antitumor activity and PK of single agent PF-06821497 in Japanese and Chinese patients. Part 2A (escalation RP2D finding for combination) will determine the MTD of the combination with SOC in patients with CRPC. Part 2B (dose expansion) will assess the efficacy of PF-06821497 at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone. The study is currently enrolling Part 2B.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Castration Resistant Prostate Cancer (CRPC)
• Small Cell Lung Cancer (SCLC)
• Follicular Lymphoma (FL)

Intervention

Drug: PF-06821497

Oral continuous

Other Name: EZH2i

Study Arms

• Experimental: Dose Escalation (Part 1A)
  Participants with SCLC, CRPC and FL will receive PF-06821497 at escalating dose levels
  Intervention: Drug: PF-06821497
• Experimental: Dose Escalation (Part 1B)
  Participants with FL will receive PF-06821497 at escalating dose levels
  Intervention: Drug: PF-06821497
• Experimental: Dose Escalation (Part 1C)
  Participants with CRPC will receive PF-06821497 at escalating dose levels.
  Intervention: Drug: PF-06821497
• Experimental: Dose Escalation (Part 2A)
  Participants with CRPC and SCLC will receive PF-06821497 at escalating dose levels in combination with SOC.
  Intervention: Drug: PF-06821497
• Experimental: Dose Expansion (Part 2B)
  Participants with CRPC will receive PF-06821497 in combination with SOC or SOC alone.
  Intervention: Drug: PF-06821497
• Experimental: Japan Cohort
  Participants with CRPC will receive PF-06821497 at one or two doses
  Intervention: Drug: PF-06821497
• Experimental: China cohort
  Participants will receive PF-06821497 at one or two doses
  Intervention: Drug: PF-06821497

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 22, 2023): 267
• Original Estimated Enrollment (submitted: March 2, 2018): 172
• Estimated Study Completion Date: September 18, 2025
• Estimated Primary Completion Date: September 18, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:

Part 1A (closed to enrollment):

Part 1B (closed to enrollment):

Part 1C:

• Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort
• Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort
• Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3)

Part 2A:

• Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3)

Part 2B:

• Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3)
• Patients must have radiographic evidence of disease

Other inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
• Adequate organ function

Key Exclusion Criteria:

- Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: CRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (CRPC): no more than 1 previous regimen of chemotherapy

• Prior irradiation to >25% of the bone marrow.
• QTcF interval >480 msec at screening.
• Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).
• Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
• Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
• Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Russian Federation, Spain, United States
• Removed Location Countries: Italy

Administrative Information

• NCT Number: NCT03460977
• Other Study ID Numbers: C2321001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: February 2023