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

Last updated on August 9, 2018

FOR MORE INFORMATION
Study Location
UC San Diego Moores Cancer Center - Investigational Drug Services
La Jolla, California, 92037-0845 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Non-Small Cell Lung Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18+ years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

Evidence of histologically or cytologically confirmed diagnosis of locally advanced or
metastatic EGFRm (del 19 or L858R) NSCLC:

1. 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).

2. 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.

3. 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.

Exclusion criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

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:

- 2 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.

- 5 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).

Partial Exclusions for Cohort 2A and 2B (Palbociclib combo):

Prior treatment with a CDK 4/6 inhibitor.

Partial Exclusions for Cohort 3 (Avelumab combo):

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

NCT02349633
Pfizer
Recruiting
Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)

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Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)
Phase 1/2 Open-label Study Of Pf-06747775 (Epidermal Growth Factor Receptor T790m Inhibitor) In Patients With Advanced Epidermal Growth Factor Receptor Mutant (Del 19 Or L858r ± T790m) Non-small Cell Lung Cancer

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).
There remains an unmet medical need to develop EGFR TKI agents that effectively target both the single activating mutations of del 19 and L858R, and the secondary resistance mutation T790M, while sparing WT EGFR. Drugs active against the resistance mutation will enable molecularly targeted therapy with a more favorable toxicity profile than the current standard of cytotoxic chemotherapy platinum based doublets. Furthermore, by having a wide margin of selectivity favoring the EGFR mutants versus WT EGFR, PF 06747775 is likely to be positioned to improve patient outcomes from an efficacy and safety perspective.
Interventional
Phase 2
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Non-Small Cell Lung Cancer
  • Drug: PF-06747775
  • Drug: Palbociclib
  • Drug: Avelumab
  • Experimental: Cohort 1
    Cohort 1 will be initiated (current dose 200 mg)
    Intervention: Drug: PF-06747775
  • Experimental: Cohort 2A
    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.
    Interventions:
    • Drug: PF-06747775
    • Drug: Palbociclib
  • Experimental: Cohort 2B
    Cohort 2B will be initiated once the RP2D of the PF-06747775 and palbociclib combination is determined.
    Interventions:
    • Drug: PF-06747775
    • Drug: Palbociclib
  • Experimental: Cohort 3
    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.
    Interventions:
    • Drug: PF-06747775
    • Drug: Avelumab
Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
159
December 17, 2021
September 2, 2020   (Final data collection date for primary outcome measure)

Partial Inclusion criteria:

Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del 19 or L858R) NSCLC:

  1. 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).
  2. 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.

  3. 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.

Partial Exclusion Criteria:

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:

  • 2 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.
  • 5 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).

Partial Exclusions for Cohort 2A and 2B (Palbociclib combo):

Prior treatment with a CDK 4/6 inhibitor.

Partial Exclusions for Cohort 3 (Avelumab combo):

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

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No

Contact: Pfizer CT.gov Call Center 1-800-718-1021 [email protected]
Australia,   Japan,   Korea, Republic of,   United States
 
 
NCT02349633
B7971001
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
December 2017

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting thte study website. To get updates and notications about this trail, sign up using the form below.

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Pfizer Clinical Trials Contact Center

1-800-718-1021

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