Tag: ACP-196

ACP-196 Displays A Favorable Safety Profile for Patients with Relapsed/Refractory CLL

Dr. Richard Furman
Dr. Richard Furman

This Phase 1/2 trial was designed to evaluate the safety profile and efficacy of orally administered ACP-196 in patients with relapsed or refractory CLL/SLL. ACP-196 is a second generation BTK inhibitor that is more selective than the first generation BTK inhibitor ibrutinib. Bruton’s tyrosine kinase (BTK) is an enzyme involved in B cell receptor pathway signaling that has been shown to be critical for CLL cell survival. Trials with ibrutinib established BTK as an effective therapeutic target for the treatment of CLL.

As part of the trial, patients were treated continuously with escalating doses of ACP-196, once or twice daily. No dose limiting toxicities were identified and 100 mg twice daily was established as the most efficacious dose. The median age of the patients and number of prior therapies were 62 years and 3 prior therapies respectively. The median time on the study was 10.3 months. As of June 2015 there were 60 patients who were evaluable for response.

The overall response rate was 93% for all patients and 100% in the deletion 17p patient. ACP-196 was well tolerated, with 93% of patients remaining on treatment. The most common adverse events were headache and diarrhea. No disease progression has occurred to date.

Results from this study show that ACP-196 is a highly potent and selective oral BTK inhibitor with a favorable safety profile. Currently there is a Phase 3 trial comparing ACP-196 to Ibrutinib in Patients with High Risk CLL open to eligible patients at Weill Cornell Medicine.

New Clinical Trial: Open-label, Phase 2 Study of ACP-196 in Subjects with Mantle Cell Lymphoma

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with mantle cell lymphoma. The study sponsor is Acerta Pharma BV, and the principal investigator at Weill Cornell is Peter Martin, M.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women greater than or equal to 18 years of age
  • Patient has confirmed Mantle Cell Lymphoma (MCL)
  • The disease has relapsed after or been refractory to at least 1 prior therapy for MCL
  • Detailed eligibility reviewed when you contact the study team

Study Details

The purpose of this study is to determine the activity of ACP-196 in subjects with relapsed or refractory MCL as measured by response rate, duration of response, progression-free survival, and time-to-next treatment.

The design and conduct of this study is supported by an understanding of the natural history and current therapies for subjects with lymphoid cancers; knowledge of the activity and safety of the first-generation Btk inhibitor (eg, ibrutinib) in subjects with hematologic cancers; and the available nonclinical and clinical information regarding ACP-196.

This study is a multicenter, open-label, randomized, parallel group study. No placebo will be administered during this study. Twenty subjects, 10 refractory and 10 relapsed, will be enrolled and will take 100 mg of ACP-196 twice per day.

This clinical trial is a Phase 2, multicenter, open-label study. Subjects will be enrolled and will take 100 mg of ACP-196 twice per day (BID) continuously for approximately 14 months. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

New Clinical Trial: An Open-label, Phase 1 Study of ACP-196 in Patients with Follicular Lymphoma

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with follicular lymphoma (FL). The study sponsor is Acerta Pharma BV, and the principal investigator at Weill Cornell is Dr. Peter Martin. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women greater than or equal to 18 years of age
  • Confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to >  or = 1 prior therapy for FL and which requires treatment
  • Detailed eligibility will be reviewed when you contact the study team

Study Details

The purpose of this study is to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and activity of 2 different schedules of ACP-196 administration in subjects with FL.

Clinical Studies have shown that targeting the B-cell receptor (BCR) signaling pathway by inhibiting Bruton tyrosine kinase (Btk) produces significant clinical benefit in patients with non-Hodgkin lymphoma including FL. Ibrutinib, a first generation Btk inhibitor, has been approved for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In addition, in a first-in-human study of ibrutinib, 6 of 16 subjects (38%) with FL had an objective response.  Acerta Pharma BV has developed a novel second generation Btk inhibitor, ACP-196, that achieves significant oral bioavailability and potency in preclinical models. ACP-196 monotherapy is currently in Phase 1 studies in subjects with CLL and in healthy volunteers.

This study is a multicenter, open-label, randomized, parallel group study. No placebo will be administered during this study. Twenty subjects will be equally randomized (1:1 ratio) into 2 cohorts. In each cohort, subjects will take 200mg of ACP-196 per day, but with different schedules of administration:

  • Cohort 1: ACP-196 100 mg/twice daily for 28 days (= 1 cycle)
  • Cohort 2: ACP-196 200 mg/once daily for 28 days (= 1 cycle)

Treatment with ACP-196 may be continued for more than 28 days until disease progression or an unacceptable drug-related toxicity occurs. Dose modification provisions are provided in the study protocol. All subjects who discontinue study drug will have a safety follow-up visit 30 (+/- 7) days after the last dose of the study drug unless they have started another cancer therapy within that time frame.