Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors

NCT04771520 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0439NCI-2021-00702
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Malignant Solid Neoplasm; Locally Advanced Melanoma; Locally Advanced Primary Malignant Central Nervous System Neoplasm; Locally Advanced Sarcoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Primary Malignant Central Nervous System Neoplasm; Metastatic Sarcoma; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR defined as confirmed complete response (CR) or partial response (PR) from the time of study treatment initiation until disease progression as centrally assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria, as appropriate. Confirmed CR or PR will be defined as a repeat assessment performed 4 weeks (+/-3 days) after the criteria for response is first met. Will estimate ORR along with 90% confidence interval according to Clopper-Pearson method for each cohort and for specific tumor type.

  or date of death from any cause, whichever came first, assessed up to 50 months

Secondary Outcomes (3)

• Duration of response (DoR)

  Up to study completion (estimated 4 years)

• Disease control rate (DCR)

  >= 16 weeks following study treatment initiation

• Incidence of adverse events

  Up to study completion (estimated 4 years)

Study Arms (1)

Treatment (avapritinib)

EXPERIMENTAL

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

Drug: Avapritinib

Interventions

Avapritinib DRUG

Given PO

Also known as: (S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1Hpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-yl)pyrimidin-5-yl)ethan-1-amine, AYVAKIT, BLU-285, CS3007, PDGFR alpha/KIT Mutant-specific Inhibitor BLU-285

Treatment (avapritinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient (or legally acceptable representative if applicable) provides written informed consent for the study.
• Male or female ≥18 years of age on the day of informed consent signing. Adolescent patients aged 12 years and older are allowed with signed assent and parental consent according to institutional guidelines and requirements.
• Cohorts 1 and 2: Patient has a locally advanced or metastatic solid tumor and has progressed on appropriate standard therapy, has not shown clinically meaningful benefit to appropriate standard therapy, has no available standard therapy, or has declined appropriate standard therapy.
• NOTE: Specific solid tumor types include but are not limited to melanoma, breast cancer, lung cancer, gastroesophageal cancer, colorectal cancer, sarcoma, solid tumors NOS, and primary CNS tumors. Patients with any other recurrent solid tumor type with the exception of gastrointestinal stromal tumor (GIST) will be eligible.
• Cohort 3: Patient has newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma. Patients must have received prior treatment with radiation and concurrent temozolomide per standard of care.27 Patients must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.
• Measurable disease per the RECIST v1.1 or RANO criteria, as appropriate, for Cohorts 1 and 2. Patients in Cohort 3 can have measurable or non-measurable disease per the RANO criteria.
• Documented pathogenic CKIT activating mutation (Cohort 1) OR pathogenic PDGFRA activating mutation (Cohort 2) based on Clinical Laboratory Improvement Amendments-certified next-generation sequencing diagnostic test. Cohort 3 should have pathogenic CKIT or PDGFRA activating mutation/amplification based on CLIA-certified NGS diagnostic test. CKIT and PDGFRA mutation pathogenicity will be verified by the MD Anderson Cancer Center's Precision Oncology Decision Support team. Acceptable CKIT/PDGFRA mutations for study eligibility are listed in Appendix E.
• \. Has available archival tissue for CKIT/PDGFRA mutation (amplification \[Cohort 3 only\]) retrospective testing.
• \. Adequate organ and marrow function as defined below within 7 days of study treatment initiation:
• White blood cell count \>2,500/µL and \<15,000/µL
• Absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
• Platelet count ≥75 × 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility)
• Hemoglobin ≥9.0 g/dL (without blood transfusion within 7 days of laboratory test used to determine eligibility)
• Total bilirubin ≤1.5 × upper limit of normal (ULN); if hepatic metastases are present, ≤3.0 × ULN
• Aspartate transaminase and alanine transaminase ≤2.5 × ULN; if hepatic metastases are present, ≤5.0 × ULN

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Patients who have GIST.
• Patients with tyrosine kinase inhibitor-resistant CKIT mutation V654A or T670I.
• Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy) are eligible (including those with untreated brain metastases). If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging scan should show no increase in brain lesion size/volume.
• History of documented congestive heart failure (New York Heart Association functional classification III-IV) or serious cardiac arrhythmias requiring treatment.
• QT interval corrected using Fridericia's formula of \>470 msec.
• Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to study treatment initiation.
• Prior anticancer chemotherapy, hormone therapy, immunotherapy, targeted therapy, radiation therapy, or surgery within 2 weeks prior to study treatment initiation.
• NOTE: Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline (except alopecia). Patients with ≤ Grade 2 neuropathy are eligible.
• NOTE: If patient received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to study treatment initiation.
• NOTE: Patients in Cohort 3 must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.
• Symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
• History of psychotic or depressive disorder. Patients whose disorder is well controlled on a stable antipsychotic or antidepressant medication for at least 12 months prior to study entry will be eligible.
• Concomitant use of a known strong cytochrome P450 (CYP)3A4 inhibitor or strong CYP3A4 inducer. The required washout period prior to study treatment initiation is 2 weeks or 5 half-lives, whichever is shortest.
• Females who are pregnant or breastfeeding.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M.D. Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma; Sarcoma; Colorectal Neoplasms; Lung Neoplasms

Interventions

avapritinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jordi Rodon Ahnert

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordi R Rodon, MD, PHD

CONTACT

(713) 792-5603; jrodon@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 25, 2021
• Study Start: January 20, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

US (1)