NCT01970865|CompletedPhase 1Results

A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations

PHASE 1/2 STUDY OF PF-06463922 (AN ALK/ROS1 TYROSINE KINASE INHIBITOR) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS

Pfizer ClinicalTrials.gov

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2 other identifiers

B74610012013-002620-17

Study Type

interventional

Target

364

Locations

14 countries

Sites

Timeline

RegisteredOct 2013

StartedJan 2014

CompletionMay 2023

Brief Summary

Phase 1 and 2 trial to study the safety, pharmacokinetics, pharmacodynamics, patient reported outcomes and efficacy of PF-06463922 in ALK + advanced non-small cell lung cancer patients and ROS1+ advanced non small cell lung cancer patients .

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

364

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Jan 2014

Longer than P75 for phase_1

Geographic Reach

14 countries

77 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.4 years study duration

First Submitted

Initial submission to the registry

October 16, 2013

Completed

12 days until next milestone

First Posted

Study publicly available on registry

October 28, 2013

Completed

2 months until next milestone

Study Start

First participant enrolled

January 8, 2014

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2017

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

May 29, 2018

Completed

5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 24, 2023

Completed

Last Updated

August 12, 2024

Status Verified

July 1, 2024

Enrollment Period

3.2 years

First QC Date

October 16, 2013

Results QC Date

March 5, 2018

Last Update Submit

July 16, 2024

Conditions

ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC

Keywords

Phase 1Phase 2safetypharmacokineticpharmacodynamicefficacy

Outcome Measures

Primary Outcomes (2)

Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1
DLT: any of following adverse events (AEs) attributable to PF-06463922: (1) hematologic: grade 4 neutropenia for \>7 days; febrile neutropenia; grade\>=3 neutropenic infection; grade\>=3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade\>=3 pancreatitis; grade\>=3 toxicities (excluding grade \>=3 laboratory abnormalities not requiring dose modifications) persisting after optimal treatment with standard medical therapy; symptomatic grade \>=3 QT interval corrected for heart rate (QTc) prolongation, or asymptomatic grade \>=3 prolongation that had been confirmed by repeat testing, re-evaluation by qualified person, persisted after correction of reversible causes; \>=20% decrease from baseline in left ventricular ejection fraction (LVEF); (3) other: failure to deliver at least 16 out of 21 prescribed daily total dose due to toxicities attributable to study drug; failure to restart dosing after 21 days (1 cycle) delay due to toxicity attributable to study drug.
Cycle 1 (21 days)
Percentage of Participants With Overall and Intracranial Objective Response (Phase 2)
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions electronic case report form (eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
3 years

Secondary Outcomes (70)

Percentage of Participants With Overall and Intracranial Objective Response (Phase 1)
From start of study treatment until CR or PR (maximum of 8 years approximately)
Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)
From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately)
Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1)
From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1)
12 and 24 weeks
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)
3 years
+65 more secondary outcomes

Other Outcomes (1)

Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study)
From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)

Study Arms (2)

PF-06463922

EXPERIMENTAL

Drug: PF-06463922

Crizotinib

OTHER

ALK+ NSCLC patients who are treatment naïve may be eligible to receive crizotinib following PF-06463922 as a substudy to the main study.

Drug: Crizotinib

Interventions

PF-06463922DRUG

Oral, starting dose 10mg once a day, dose escalation in Phase 1 until recommended Phase 2 dose determined, continuous daily dosing, cycles lasting 21 days

PF-06463922

CrizotinibDRUG

Oral, starting dose of 250 mg BID continuous daily dosing every 21 days

Also known as: Xalkori

Crizotinib

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
Disease Status Requirements:
Phase 1: ALK-positive NSCLC and ROS1-positive patients must either be treatment naïve in the advanced setting or have had disease progression after at least 1 previous ALK/ROS1 inhibitor therapy(ies).
Phase 2:
ALK-positive NSCLC patients must either be or have had:
Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed).
Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting.
Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting.
Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting.
Disease progression after 2 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.
Disease progression after 3 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.
ROS1-positive NSCLC patients may be:
Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy).
Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).
Tumor Requirements:
+2 more criteria

You may not qualify if:

Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
Systemic anti cancer therapy completed within a minimum of 5 half lives of study entry.
Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
Clinically significant cardiovascular disease (that is, active or \<3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), second-degree or third-degree AV block (unless paced) or any AV block with PR \>220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc \>470 msec, or congenital long QT syndrome.
History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis.
Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (77)

Highlands Oncology Group/Research

Fayetteville, Arkansas, 72703, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Chao Family Comprehensive Cancer Center

Orange, California, 92868-3201, United States

Location

UC Irvine Medical Center

Orange, California, 92868-3201, United States

Location

University of Colorado Cancer Center