Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphosarcoma

Patients receive AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547

Young Kwang Chae

This phase II MATCH treatment trial identifies the effects of AZD4547 in patients whose cancer has genetic changes called FGFR gene alterations. AZD4547 may stop the growth of cancer cells by blocking FGFR proteins which may be needed for cell growth. Researchers hope to learn if AZD4547 will shrink this type of cancer or stop its growth.

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive FGFR inhibitor AZD4547 (AZD4547) orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)

MATCH Treatment Subprotocol W: Phase II Study of AZD4547 in Patients With Tumors With Aberrations in the FGFR Pathway

Overall response rate was defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

National Cancer Institute (NCI)

All 52 patients enrolled to the trial were monitored for mortality. Of the 50 patients who received protocol therapy, 49 were evaluable for AEs (1 patient had no toxicity data)

Patients receive AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547: Given PO

Treatment (AZD4547)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Statistician

Overall Response Rate (ORR)

6-month Progression-free Survival (PFS) Rate

Progression Free Survival (PFS)

Overall Study

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Crouzon Syndrome

Jackson-Weiss Syndrome

Pfeiffer Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, participants may be eligible to re-register to Arm III.

-closed to accrual 12/18/2015

Participants in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Vassiliki Papadimitrakopoulou

This phase II/III trial studies how well FGFR inhibitor AZD4547 (AZD4547) works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the fibroblast growth factor receptor (FGFR) biomarker. FGFR can cause tumor cells to grow more quickly. AZD4547 may decrease the activity of FGFR and may be able to shrink tumors.

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the Phase III component by evaluating the objective response rate (ORR) with AZD4547 in FGFR-positive patients. (Phase II) II. If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized Phase III trial. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in FGFR-positive patients treated with AZD4547. (Phase II) II. To evaluate the duration of response (DoR) among FGFR positive patients treated with AZD4547 who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II) III. To evaluate the frequency and severity of toxicities associated with AZD4547 in FGFR positive patients. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the AZD4547 beyond the chosen biomarker for biomarker-driven sub-studies.

II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/ blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung.

OUTLINE: As of 12/18/2015, patients are assigned to Arm I.

ARM I: Patients receive FGFR inhibitor AZD4547 orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.

ARM III: Patients in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer

A Phase II Study of AZD4547 for Previously Treated FGFR-Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

Will be monitored by the percentage of screened patients that register to a therapeutic sub-study.

Will be monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to receive.

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with AZD4547 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review, or symptomatic deterioration or death due to any cause among patients who achieve complete or partial response per RECIST v1.1.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration on study until death from any cause. Observations for participants last known to be alive were censored.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

Adverse Events (AEs) are reported per CTCAE Version 5.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

SWOG Cancer Research Network

34 participants were assessed for AEs: 27 on AZD4547 and 9 on docetaxel arm. 2 participants that were re-registered from the docetaxel arm to receive AZD4547 after progression were assessed for AEs in both arms.

Adverse Events (AEs) are reported per CTCAE Version 5.0

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547: Given PO Laboratory Biomarker Analysis: Correlative studies

AZD4547

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, participants may be eligible to re-register to AZD4547.

Docetaxel: Given IV Other Names: Docecad Docetaxel RP56976 Taxotere Taxotere Injection Concentrate

Laboratory Biomarker Analysis: Correlative studies

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547: Given PO

Laboratory Biomarker Analysis: Correlative studies

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to AZD4547.

Docetaxel Given IV

Other Names:

* Docecad
* Docetaxel
* RP56976
* Taxotere
* Taxotere Injection Concentrate

Laboratory Biomarker Analysis: Correlative studies

Total

Black

White

Hispanic

Race/Ethnicity, Customized

Participants were graded according to the Zubrod Performance Status Scale.

0 - Fully active, able to carry out on all pre-disease performance without restriction.

1. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work.
2. - Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.

Performance status

Docetaxel arm closed before data were collected

Number of prior lines of therapy for stage IV disease

Smoking status

Lung Committee Statistician

Arm I - AZD4547

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)

Eligible and evaluable participants that achieved complete response or partial response.

Duration of Response Among Patients Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1

Overall Survival

Progression-free Survival

Dyspnea

Fatigue

Febrile neutropenia

Hyponatremia

Lung infection

Lymphocyte count decreased

Mucositis oral

Neutrophil count decreased

Retinopathy

Sepsis

White blood cell decreased

Participants who received at least one dose of AZD4547 treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)	NCT04439240	Advanced Lympho... Advanced Malign... Hematopoietic a... Refractory Lymp... Refractory Mali... Refractory Plas...	FGFR Inhibitor ...	18 Years -	National Cancer Institute (NCI)
Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W)	NCT04439240	Advanced Lympho... Advanced Malign... Hematopoietic a... Refractory Lymp... Refractory Mali... Refractory Plas...	FGFR Inhibitor ...	18 Years -	National Cancer Institute (NCI)
Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer	NCT02965378	FGFR1 Gene Ampl... FGFR1 Gene Muta... FGFR2 Gene Ampl... FGFR2 Gene Muta... FGFR3 Gene Ampl... FGFR3 Gene Muta... Recurrent Squam... Stage IV Squamo...	Docetaxel FGFR Inhibitor ... Laboratory Biom...	25 Years -	SWOG Cancer Research Network

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