NCT04439240

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

Completed Phase 2 Results posted Last updated 29 June 2021

What this trial tests

Phase 2 trial testing FGFR Inhibitor AZD4547 in Advanced Lymphoma in 52 participants. Completed in 30 June 2020.

Timeline

31 May 2016

Primary endpoint
6 June 2019

30 June 2020

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	52
Start date	31 May 2016
Primary completion	6 June 2019
Estimated completion	30 June 2020
Sites	1 location across United States

Drugs / interventions tested

• FGFR Inhibitor AZD4547 — full drug profile →

Conditions studied

• Advanced Lymphoma — all drugs for Advanced Lymphoma →
• Advanced Malignant Solid Neoplasm — all drugs for Advanced Malignant Solid Neoplasm →
• Hematopoietic and Lymphoid Cell Neoplasm — all drugs for Hematopoietic and Lymphoid Cell Neoplasm →
• Refractory Lymphoma — all drugs for Refractory Lymphoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Advanced Lymphoma or Advanced Malignant Solid Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration

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.

Group	Value	95% CI
Treatment (AZD4547)	8	3 – 18

6-month Progression-free Survival (PFS) Rate Secondary · Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS is determined

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.

Group	Value	95% CI
Treatment (AZD4547)	15	8 – 31

Progression Free Survival (PFS) Secondary · Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration

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.

Group	Value	95% CI
Treatment (AZD4547)	3.4	1.8 – 4.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (AZD4547)

Serious: 19/49 (39%)

Deaths: 44/52

Serious adverse events (21 terms)

Reaction	System	Treatment (AZD4547)
Mucositis oral	Gastrointestinal disorders	—
Aspartate aminotransferase increased	Investigations	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—
Alanine aminotransferase increased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Abdominal pain	Gastrointestinal disorders	—
Constipation	Gastrointestinal disorders	—
Esophageal pain	Gastrointestinal disorders	—
Small intestinal obstruction	Gastrointestinal disorders	—
Sepsis	Infections and infestations	—
GGT increased	Investigations	—
Neutrophil count decreased	Investigations	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Hypophosphatemia	Metabolism and nutrition disorders	—
Dizziness	Nervous system disorders	—
Peripheral sensory neuropathy	Nervous system disorders	—
Syncope	Nervous system disorders	—
Dry eye	Eye disorders	—
Laryngeal mucositis	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (38 terms — click to expand)

Reaction	System	Treatment (AZD4547)
Dry mouth	Gastrointestinal disorders	—
Fatigue	General disorders	—
Mucositis oral	Gastrointestinal disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Anorexia	Metabolism and nutrition disorders	—
Constipation	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Dry eye	Eye disorders	—
Vomiting	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Alkaline phosphatase increased	Investigations	—
Dysgeusia	Nervous system disorders	—
Eye disorders - Other, specify	Eye disorders	—
Anemia	Blood and lymphatic system disorders	—
Dry skin	Skin and subcutaneous tissue disorders	—
Nail discoloration	Skin and subcutaneous tissue disorders	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—
Weight loss	Investigations	—
Nail loss	Skin and subcutaneous tissue disorders	—
Alanine aminotransferase increased	Investigations	—
Creatinine increased	Investigations	—
White blood cell decreased	Investigations	—
Hypercalcemia	Metabolism and nutrition disorders	—
Blurred vision	Eye disorders	—
Aspartate aminotransferase increased	Investigations	—
Lymphocyte count decreased	Investigations	—
Hyponatremia	Metabolism and nutrition disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Dyspepsia	Gastrointestinal disorders	—
Blood bilirubin increased	Investigations	—
Neutrophil count decreased	Investigations	—
Hypomagnesemia	Metabolism and nutrition disorders	—
Hypophosphatemia	Metabolism and nutrition disorders	—
Peripheral sensory neuropathy	Nervous system disorders	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Mucositis oral, Aspartate aminotransferase increased, Palmar-plantar erythrodysesthesia syndrome, Alanine aminotransferase increased, Anemia, Febrile neutropenia, Abdominal pain, Constipation.

Data from ClinicalTrials.gov NCT04439240 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention.
   De Luca A, Esposito Abate R, Rachiglio AM, Maiello MR, et al · · 2020 · cited 87× · PMID 32962091 · DOI 10.3390/ijms21186856
2. Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review.
   Zheng J, Zhang W, Li L, He Y, et al · · 2022 · cited 50× · PMID 35494629 · DOI 10.3389/fchem.2022.860985
3. FGF/FGFR Signaling in Hepatocellular Carcinoma: From Carcinogenesis to Recent Therapeutic Intervention.
   Wang Y, Liu D, Zhang T, Xia L. · · 2021 · cited 48× · PMID 33802841 · DOI 10.3390/cancers13061360
4. Molecular and immunological mechanisms of clonal evolution in multiple myeloma.
   Forster S, Radpour R, Ochsenbein AF. · · 2023 · cited 22× · PMID 37744361 · DOI 10.3389/fimmu.2023.1243997
5. Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors.
   Bao Y, Gabrielpillai J, Dietrich J, Zarbl R, et al · · 2021 · cited 21× · PMID 34933671 · DOI 10.1186/s13148-021-01212-4
6. MYC inhibitors in multiple myeloma.
   Martínez-Martín S, Soucek L. · · 2021 · cited 19× · PMID 35582389 · DOI 10.20517/cdr.2021.55
7. Where We Stand With Precision Therapeutics in Myeloma: Prosperity, Promises, and Pipedreams.
   Pan D, Richter J. · · 2021 · cited 15× · PMID 35127532 · DOI 10.3389/fonc.2021.819127
8. Molecularly Guided Drug Repurposing for Cholangiocarcinoma: An Integrative Bioinformatic Approach.
   Venkatraman S, Balasubramanian B, Pongchaikul P, Tohtong R, et al · · 2022 · cited 12× · PMID 35205315 · DOI 10.3390/genes13020271