Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)

NCT02349633 | Terminated Phase 1 Results

• 1 other identifier: B7971001
• Study Type: interventional
• Target: 65
• Locations: 4 countries
• Sites: 15

Brief Summary

This is a Phase 1/2 study of PF-06747775 as a single agent and in combination with other cancer treatments in patients with advanced EGFRm NSCLC. The overall clinical study consists of a Phase 1 single agent dose-escalation and expansion part to determine the RP2D of PF-06747775 single agent in patients with previously-treated EGFRm NSCLC followed by sequential evaluations of PF-06747775 at the RP2D in 3 different clinical scenarios as detailed below:

• Cohort 1: Phase 2 evaluation of PF-06747775 as a single agent in previously untreated patients with advanced EGFRm NSCLC,
• Cohort 2: Phase 1b single arm evaluation of PF-06747775 in combination with palbociclib (Cohort 2A) followed by Phase 2 randomized evaluation of PF 06747775 in combination with palbociclib vs PF-06747775 single agent (Cohort 2B) in previously-treated patients with EGFRm NSCLC with a secondary T790M mutation (del 19 and T790M or L858R and T790M), and
• Cohort 3: Phase 1b evaluation of PF-06747775 in combination with avelumab in previously-treated patients with EGFRm NSCLC with a secondary T790M mutation (del 19 and T790M or L858R and T790M).

Conditions

Non-Small Cell Lung Cancer

Keywords

EGFRm - Epidermal Growth Factor Receptor Mutation; Advanced EGFRm (del19 or L858R +/- T790M NSCLC

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle in Phase 1 Dose-escalation Cohorts, Japan LIC and Phase 1b Cohort 3, and First 2 Cycles in Phase 1b Cohort 2A

  DLT was defined as any of the following adverse events (AEs) occurring during the first cycle for Phase 1 dose-escalation cohorts, Japan LIC and Phase 1b Cohort 3, or the first 2 cycles for Phase 1b Cohort 2A of treatment, and considered attributable to study intervention: Grade 4 neutropenia \>7 days; febrile neutropenia; Grade \>=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade \>=3 non-hematologic toxicities; Grade 4 rash, mucositis, or diarrhea; failure to receive at least 70% of planned doses; Grade 3 QTcF prolongation in asymptomatic participants; treatment-related AEs attributable to PF-06747775, palbociclib or both that caused palbociclib treatment delay \>= 10 days or omission of at least 12 doses of the combination. Grade of AE was defined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

  21 days for Phase 1 dose-escalation cohorts and Japan LIC; 42 days for Phase 1b Cohort 2A; 28 days for Phase 1b Cohort 3

• Number of Participants With Confirmed Objective Response (OR) in PF-06747775 200 mg QD Group

  Number of participants with confirmed OR according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. Complete response (CR) was defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) was defined as Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.

  Baseline up to end of treatment (maximum of 165 weeks)

• Progression-free Survival (PFS) in Phase 2 Cohort 2B

  PFS was based on Kaplan-Meier estimates. PFS was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective progression (PD) or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.

  Cycle 1 Day 1 up to the end of study (maximum of 5 years)

Secondary Outcomes (55)

• Number of Participants With Treatment-emergent AEs (TEAEs) in All Cohorts All Phases (All-causality)

  Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)

• Number of Participants With TEAEs in All Cohorts All Phases (Treatment-related)

  Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)

• Number of Participants With Serious Adverse Events (SAEs) in All Cohorts All Phases

  Baseline up to 28 days after last dose of study treatment (maximum of 199 weeks)

• Number of Participants With Shifts of Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline in All Cohorts All Phases

  Baseline up to the end of treatment (maximum of 195 weeks)

• Number of Participants Meeting Categorical Criteria of QTcF Values When PF-06747775 Was Given as a Single Agent, and in Combination With Palbociclib and Avelumab.

  Baseline up to Cycle 4 Day 1 (maximum of 10 weeks)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Cohort 1 will be initiated (current dose 200 mg)

Drug: PF-06747775

Cohort 2A

EXPERIMENTAL

Cohort 2A will evaluate PF-06747775 200 mg by mouth (PO) daily (QD) in combination with palbociclib continuous PO QD dosing in 21-day cycles. The starting dose (DL1) for palbociclib will be 100 mg PO daily. Dose finding will follow mTPI method with adjustments using DLT rate.

Drug: PF-06747775; Drug: Palbociclib

Cohort 2B

EXPERIMENTAL

Cohort 2B will be initiated once the RP2D of the PF-06747775 and palbociclib combination is determined.

Drug: PF-06747775; Drug: Palbociclib

Cohort 3

EXPERIMENTAL

Cohort 3 combination is PF-06747775 200 mg PO QD and avelumab 10 mg/kg IV Q2W in 28-day (4-week) cycles. Dose finding will follow the mTPI design. Once RP2D of PF-06747775 in combination with avelumab is determined, the Dose Expansion Phase will be opened.

Drug: PF-06747775; Drug: Avelumab

Interventions

PF-06747775 DRUG

Cohort 1; Cohort 2A; Cohort 2B; Cohort 3

Palbociclib DRUG

Cohort 2A; Cohort 2B

Avelumab DRUG

Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del 19 or L858R) NSCLC:
• As detected by local EGFR mutation test that includes QIAGEN therascreen EGFR RGQ PCR kit, Roche cobas® EGFR Mutation Test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory (with tissue submitted for central laboratory confirmation via FDA approved QIAGEN therascreen RCQ PCR kit).
• T790M disease as follows:
• Phase 1 If a repeat biopsy was performed on the tumor following prior EGFR TKI therapy, then T790M positive disease must be present. Patients of unknown T790M status following EGFR TKI progression (ie, no post EGFR TKI progression biopsy was performed) are eligible.
• In the PK sub-studies involving food/antacid and CYP3A4 effects, patients with EGFRm (del 19 or L858R) with any T790M status are eligible to enroll.
• Studies at RP2D Cohort 1: Patients may have de novo T790M mutation, but it is not required. Cohort 2 and Cohort 3: Patients must have EGRFm (del 19 AND T790M or L858R AND T790M) NSCLC tumors as detected by local EGFR mutation test that includes QIAGEN Therascreen EGFR RGQ PCR kit, Roche cobas® EGFR Mutation Test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory, which will then be retrospectively confirmed by the central validated Thermo Fisher Scientific Oncomine Next Generation Sequencing (NGS) cancer panel test. Patients will also be enrolled if they solely test positive for EGFR (del 19 AND T790M or L858R AND T790M) NSCLC in plasma detected by local EGFR mutation test that includes QIAGEN Therascreen EGFR Plasma RGQ kit, Roche cobas® EGFR mutation test v2 (US-IVD) or Sysmex Inostic's OncoBEAMTM EGFR test or a sponsor-approved laboratory developed test that is validated in a CLIA laboratory, which will then be retrospectively confirmed by a validated cfDNA test as determined by the Sponsor.
• Prior treatment for EGFRm NSCLC as follows:
• Phase 1 Has progressed after at least 1 prior line of therapy including and EGFR TKI. Patients may have also received other lines of therapy before or after the EGFR TKI.
• Studies at RP2D Cohort 1: no prior treatment for locally advanced or metastatic EGFRm NSCLC. Cohorts 2 and 3: must have had disease progression on treatment with an approved 1st or 2nd generation EGFR TKI. Patients who have been treated with a 3rd generation EGFR TKI are ineligible for this study. Patients may have had multiple lines of therapy; however, the last therapy prior to study treatment must have been an approved EGFR TKI and received within 6 weeks prior to study registration.
• Patients must have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
• Tumor tissue available. Requesting formalin fixed paraffin embedded (FFPE) block or 15 unstained sections (5 micron). If a lesser amount of tissue is available, contact the sponsor. An archival specimen is acceptable for Phase 1; a de novo specimen is required for Cohorts 2, and 3 if the T790M status was confirmed by tissue biopsy.

You may not qualify if:

• For All Phases/Cohorts Previously diagnosed brain metastases, unless the patient has completed the treatment that is clinically indicated, if any, and has recovered from the acute effects of any treatment that was delivered prior to study registration, have discontinued corticosteroid treatment for these metastases prior to registration, and are neurologically stable.
• Major surgery within 2 weeks prior to registration.
• Radiation therapy, excluding stereotactic radiosurgery (SRS), within 1 week prior to registration.
• Systemic anti cancer therapy within 2 weeks or 5 half-lives (whichever is longer) of registration excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a minimum of:
• days prior to registration for erlotinib or afatinib, or 3 days for gefitinib if they will be part of the lead-in single dose PF-06747775 PK study (Phase 1 Dose Escalation Single and Multiple dose PK and ECG Assessments; Phase 1 Sildenafil at MTD; and Phase 1b/2 First-Line Single Agent). Please contact the Sponsor for direction for any other EGFR TKI.
• half-lives or 5 days (whichever is longer) prior to registration if they will be starting on continuous PF-06747775 dosing directly (Phase 1 PK sub-studies at RP2D; Phase 1b/2 Combination with Palbociclib; Phase 1b Combination with Avelumab).
• Prior treatment with a CDK 4/6 inhibitor.
• Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Use of immunosuppressive medication at time of randomization

Sponsors & Collaborators

• Pfizer: lead

Study Sites (15)

UC San Diego Medical Center - La Jolla

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Prince Charles Hospital, Cancer Care Services

Chermside, Queensland, 4032, Australia

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location

Seoul National University Hospital / Department of Internal Medicine

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

palbociclib; avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 29, 2015
• Study Start: May 14, 2015
• Primary Completion: May 28, 2020
• Study Completion: May 28, 2020
• Last Updated: June 10, 2021
• Results First Posted: June 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); AU (3); US (7); JP (2)