FDA Pipeline: Designation in CLL, New Drug Application in GIST, New Prostate Ablation System Receives 510(k) Clearance


Recently, the U.S. Food and Drug Administration granted Breakthrough Therapy designation to acalabrutinib in chronic lymphocytic leukemia (CLL), accepted a new drug application for avapritinib in some types of gastrointestinal stromal tumors (GIST), and granted 501(k) clearance to market the TULSA-PRO for ablation of prostate tissue.

Breakthrough Therapy Designation for Acalabrutinib in Chronic Lymphocytic Leukemia

The FDA granted Breakthrough Therapy designation to acalabrutinib as a monotherapy treatment for adult patients with chronic lymphocytic leukemia (CLL).

Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor. Acalabrutinib binds covalently to BTK, thereby inhibiting its activity.

The FDA granted the designation based on positive results from the interim analyses of the ELEVATE-TN and ASCEND phase III clinical trials. Together the trials showed that acalabrutinib alone or in combination significantly increased the time patients lived without disease progression or death, with safety and tolerability that was consistent with its established profile.


ELEVATE-TN (ACE-CL-007) is a randomized, multicenter, open-label phase III trial evaluating the safety and efficacy of acalabrutinib alone or in combination with obinutuzumab vs chlorambucil in combination with obinutuzumab in previously untreated patients with CLL. In the trial, 535 patients were randomly assigned (1:1:1) to three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab; patients in the second arm received acalabrutinib (100 mg twice daily until disease progression or unacceptable toxicity) in combination with obinutuzumab; and patients in the third arm received acalabrutinib monotherapy (100 mg twice daily until disease progression or unacceptable toxicity).

The primary endpoint is progression-free survival (PFS) in the acalabrutinib and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the acalabrutinib monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment, and overall survival.


ASCEND (ACE-CL-309) is a global, randomized, multicenter, open-label phase III trial evaluating the efficacy of acalabrutinib in previously treated patients with CLL. In the trial, 310 patients were randomly assigned (1:1) to two arms. Patients in the first arm received acalabrutinib monotherapy (100 mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received physician’s choice of either rituximab in combination with idelalisib or rituximab in combination with bendamustine.

The primary endpoint is PFS assessed by an IRC, and key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as overall survival, patient-reported outcomes, and time to next treatment.3

New Drug Application for Avapritinib for the Treatment of PDGFRA Exon 18–Mutant GIST and Fourth-Line GIST

The FDA accepted a new drug application for avapritinib in the treatment of adult patients with PDGFRA exon 18–mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST. The FDA granted Priority Review and set an action date of February 14, 2020 under the Prescription Drug User Fee Act (PDUFA). Previously, the FDA granted avapritinib Breakthrough Therapy designation for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation.

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT- and PDGFRA-mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

510(k) Clearance for TULSA-PRO for Ablation of Prostate Tissue

The FDA granted 510(k) clearance to market TULSA-PRO for ablation of prostate tissue.

TULSA-PRO is a transurethral prostate tissue ablation system that combines real-time magnetic resonance imaging with robotically-driven directional thermal ultrasound and closed-loop temperature feedback control software to deliver predictable physician-prescribed ablation of whole-gland or partial prostate tissue. The TULSA-PRO system is designed to provide customizable and predictable, incision-free, and radiation-free prostate ablation while actively protecting the urethra and rectum with water cooling to preserve men’s functional abilities.

The FDA’s clearance of TULSA-PRO was based on the TACT clinical trial, which met all of its primary and secondary efficacy and safety endpoints. TACT enrolled 115 patients across the United States, Canada, and Europe with biopsy-proven, organ-confined prostate cancer (67% and 33% of subjects had National Comprehensive Cancer Network® intermediate- and low-risk disease, respectively). All patients received primary treatment of whole-gland prostate ablation with sparing of the urethra and urinary sphincter.

TACT demonstrated that the TULSA-PRO provided safe and effective prostate tissue ablation, with minimal adverse events, significant prostate volume and prostate-specific antigen reduction, and low rates of residual prostate disease. The favorable safety profile offered by the TULSA-PRO contrasts with radical prostatectomy and radiation therapy that can leave many men with permanent erectile dysfunction, urinary incontinence, and bowel dysfunction. The TACT study also demonstrated a favorable risk-benefit profile in the context of other ablative approaches, including whole-gland high-intensity focused ultrasound and cryotherapy.

The FDA label for TULSA-PRO will allow surgeons in the United States to perform prostate tissue ablation procedures indiscriminate of tissue type, including malignant and benign.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.