AzTrials
AzTrials

ALK-positive Advanced NSCLCPhase 1NCT02511184

Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients

A Phase 1 study testing Crizotinib and Pembrolizumab in people with ALK-positive Advanced NSCLC, run by Pfizer at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ALK-positive Advanced NSCLC
What is being tested?
Crizotinib and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
15 sitesUnited States
Study dates
Oct 2015to Dec 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment.
  • Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test.
  • No prior systemic therapy for metastatic disease.
  • Adjuvant chemotherapy more than 12 months prior to study enrollment.
  • Measurable disease as per RECIST 1.1
  • ECOG PS 0 or 1.

Who cannot join

  • Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways.
  • known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other form of immunosuppressive therapy within 7 days of clinical trial treatment.
  • Active autoimmune disease that has required systemic treatment in the past 3 months.
  • History of extensive disseminated interstitial fibrosis or any grade of interstitial lung disease.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • The Emory Clinic

    Atlanta, Georgia, 30322

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham, IDS Pharmacy

    Birmingham, Alabama, 35249

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • City of Hope National Medical Center

    Duarte, California, 91010

  • UC San Diego Moores Cancer Center - Investigational Drug Services

    La Jolla, California, 92037-0845

  • UC San Diego Medical Center - La Jolla(Thornton Hospital)

    La Jolla, California, 92037

  • University Of California / San Diego Moores Cancer Center

    La Jolla, California, 92093

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Swedish Investigational Drug Services Pharmacy

    Seattle, Washington, 98104

Other trials in United States

About this study

Official title: A PHASE 1B STUDY OF CRIZOTINIB IN COMBINATION WITH PEMBROLIZUMAB (MK-3475) IN PATIENTS WITH UNTREATED ADVANCED ALK-TRANSLOCATED NON SMALL CELL LUNG CANCER

The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination.

Read the detailed description

The patients will be screened for up to 28 days before they start treatment to determine if they meet eligibility criteria. The screening procedures will include physical examination, blood work and radiological scans.

In the dose finding phase, patients who meet eligibility criteria will receive crizotinib at the dose level assigned that will be taken on daily basis and pembrolizumab 200 mg intravenous infusion every 3 weeks.

Once a Crizotinib dose level is decided, the dose expansion cohort will start enrolling patients who meet eligibility criteria.

All patients will be followed up every three weeks. Blood samples will be drawn to test for safety and tumor activities and radiological scans will be performed on certain timepoints to determine the antitumor activities.

There will be a quality of life questionnaire administered at certain time points during the study.

The study will have a quality assurance plan that addresses data validation and registry procedures. There is a plan to visit the investigator site for routine monitoring and auditing.

The team will conduct source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (e.g., medical records, paper or electronic case report forms, or interactive voice response systems).

The study will also include a statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives of this study, as specified in the study protocol or statistical plan.

Being tested
Crizotinib, Pembrolizumab
Keywords
crizotinib, pembrolizumab, ALK-positive NSCLC, Lung Cancer, ALK-translocated NSCLC, Non Small Cell Lung Cancer
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CrizotinibDrug

    To test 3 dose levels of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks

  • PembrolizumabDrug

    To test pembrolizumab at 200 mg every 3 weeks in combination with crizotinib at 3 dose levels.

Study groups in NCT02511184
Study groupRoleWhat they receive
Dose finding and dose expansion phasesExperimentalFind and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks.
Receives: Drug: Crizotinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-limiting Toxicity (DLT)

    Dose-limiting toxicity (DLT) was defined as any of the following adverse events (AEs) occurring in the first 2 cycles of treatment (6 weeks) which were attributable to crizotinib, pembrolizumab or both: hematologic toxicities including Grade 4 neutropenia, febrile neutropenia, Grade greater than or equal to (>=) 3 neutropenic infection, Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; non-hematologic toxicities including Grade >=3 toxicities (non-laboratory), Grade >=3 nausea, vomiting, or diarrhea despite maximal therapy, non-hematologic Grade >=3 laboratory value if medical intervention was required to treat the participant or the abnormality led to hospitalization; inability to complete at least 80 percent of the first 2-cycle doses of crizotinib or both infusions of pembrolizumab within the DLT observation period due to treatment-related toxicity. Grade was based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 4.03.

    Measured: 6 weeks

Secondary outcomes (32)

  1. Number of Participants With Treatment-Emergent Adverse Events

    AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: 2 years

  2. Objective Response Rate (ORR)

    ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-progressive disease (PD) or not evaluated, and no new lesions. For target lesions, CR: complete disappearance of all target lesions; PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be non-pathological in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.

    Measured: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

  3. Duration of Response

    Duration of Response (DR) was defined as the time from first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of objective tumor progression or to death on study due to any cause, whichever occurred first.

    Measured: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

  4. Time to Tumor Response

    Time to Tumor Response (TTR) was defined as the time from the first dose of crizotinib or pembrolizumab to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.

    Measured: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

  5. Progression Free Survival

    Progression Free Survival (PFS) was defined as the time from the first dose of crizotinib or pembrolizumab to the first documentation of objective tumor progression or death on-study due to any cause, whichever occurred first. For participants who did not have documented objective progression during the study or were alive at last contact, the date of last contact was used.

    Measured: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

  6. 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities

    PFS probabilities were defined as the probability of being alive and progression free at 6, 12 and 18 months after the date of first dose based on the Kaplan Meier estimate.

    Measured: Month 6, Month 12, and Month 18

  7. Overall Survival

    Overall Survival (OS) was defined as the time from the first dose of crizotinib or pembrolizumab to the date of death due to any cause. For participants who were alive at last contact, the date of last contact was used.

    Measured: Day 1 to end of study (for about 2 years)

  8. 12-Month and 18-Month Overall Survival Probabilities

    OS probabilities were defined as the probability of being alive at 12 and 18 months after the date of first dose based on the Kaplan Meier estimate.

    Measured: Month 12 and Month 18

  9. Number of Participants With Maximum Grade in Laboratory Hematology Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment

    Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Hematology test results were graded by NCI CTCAE version 4.03.

    Measured: 2 years

  10. Number of Participants With Maximum Grade in Laboratory Chemistry Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment

    Chemistry evaluation included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate, thyroid function tests including thyroid-stimulating hormone, T3 and free T4. Chemistry test results were graded by NCI CTCAE version 4.03.

    Measured: 2 years

  11. Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  12. Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  13. Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib + Pembrolizumab" Group

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  14. Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  15. Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib + Pembrolizumab" Group

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  16. Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  17. Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib + Pembrolizumab" Group

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  18. Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  19. Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib + Pembrolizumab" Group

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  20. Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  21. Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  22. Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  23. Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  24. Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  25. Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  26. Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  27. Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  28. Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  29. Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

  30. Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

    PF-06260182 is a metabolite of crizotinib.

    Measured: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

  31. Serum Concentration of Pembrolizumab

    Measured: Prior to and at end of pembrolizumab infusion, 120 hours and 336 hours post Day 1 dosing of Cycle 1; pre-dose on Day 1 of Cycles 2, 4,6, 8, 12 and 16; end of Day 1 dosing of Cycle 8; End of Treatment visit

  32. Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria

    Archived formalin-fixed, paraffin-embedded tumor issue block was collected at screening. PD-L1 assessment was performed using immunohistochemistry. A sample was considered negative if tumor proportion score was less than 1%; positive if tumor proportion score was greater than or equal to 1%; strong positive if tumor proportion score was greater than or equal to 50%.

    Measured: Screening

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2015 (estimated)
  2. Study startOct 2015
  3. Primary completionDec 2017
  4. Study completionDec 2017

Why it stopped: Decision based on the low enrollment mainly due to high efficacy drugs available in 1st line ALK-positive NSCLC (eg alectinib), not due to any safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02511184
Sponsor's protocol ID
A8081054
Other IDs
KEYNOTE 050, CRIZOTINIB
Status last verified
Apr 2019
First submitted
22 Jul 2015
Last updated
1 Jul 2019
Data monitoring committee
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crizotinib and Pembrolizumab in people with ALK-positive Advanced NSCLC, run by Pfizer at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicity (DLT) (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02511184.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in