With the TFR clinical trial program for TASIGNA, Novartis continues its commitment to transform the treatment of CML

Evaluating >1000 patients with Ph+ CML and comprising the largest set of global studies assessing TKI discontinuation1-5

ENESTfreedom is the largest frontline TFR study for TASIGNA (n=190 entered TFR phase) and also the second-largest frontline CML study overall.2 ENESTop is the largest prospective TFR study in patients who switched to TASIGNA from imatinib (n=126 entered the TFR phase).3

FIRST-LINE DATA

In ENESTfreedom, more than half of patients who met stringent eligibility criteria on frontline TASIGNA were able to remain in TFR after stopping therapy1,2

  • As the prespecified statistical null hypothesis (TFR rate ≤50%) could not be rejected due to the lower limit of the 95% CI being ≤50%, the primary endpoint failed statistically2
  • Patients who met TFR eligibility criteria had a relatively short duration of prior first-line TASIGNA use. The median treatment duration, prior to treatment discontinuation was 3.6 years1,2

Nearly 100% of patients who lost MMR after stopping treatment regained response after promptly re-initiating TASIGNA1,2

88% of patients (76/86) who lost DMR regained MR4.5 after re-initiation of TASIGNA1,2

  • Close monitoring is an important requirement of TFR1,2
  • Molecular response was tested using IS RQ-PCR every 4 weeks for 1 year, then every 6 weeks for the following year, and every 12 weeks thereafter. Prompt re-initiation of therapy is necessary if a patient loses MMR1,2
  • Upon loss of MMR patients who re-initiate TASIGNA therapy should have their BCR-ABL transcript levels monitored monthly until MMR is re-established and every 12 weeks thereafter
  • Upon the loss of MR4.0 during the treatment-free phase, BCR-ABL transcript levels were monitored every 2 weeks until BCR-ABL levels returned to a range between MR4.0 and MR4.5 or until BCR-ABL levels remained lower than MMR for 4 consecutive measurements1,2

SECOND-LINE DATA

In ENESTop, more than half of patients who met stringent eligibility criteria on second-line TASIGNA were able to remain in TFR after stopping therapy1,3

  • The study met the primary efficacy endpoint, the proportion of patients with successful TFR at 48 weeks1,3
  • Patients were on TKI therapy for a median of 7.3 years prior to discontinuation. Within this 7.3 years, patients were on TASIGNA a median of 4.4 years prior to discontinuation3

Nearly 100% of patients who lost MR4.0 or MMR after stopping treatment regained molecular responses after promptly re-initiating TASIGNA1,3

92.2% (47/51) were able to regain MR4.5 after re-initiation of TASIGNA1,3

  • Close monitoring is an important requirement of TFR.
  • Prompt re-initiation of therapy is necessary if a patient loses MMR or with confirmed loss of MR4.01,3
  • Molecular response was tested using IS RQ-PCR every 4 weeks for 1 year, then every 6 weeks for the following year, and every 12 weeks thereafter1,3
  • Patients with confirmed loss of MR4.0 during the treatment-free phase (2 consecutive measures separated by at least 4 weeks showing loss of MR4.0) or loss of MMR must re-initiate treatment within 4 weeks of when loss of remission is known to have occurred. TASIGNA therapy should be re-initiated at either 300 mg or 400 mg twice daily.
  • Patients who re-initiate TASIGNA therapy should have their BCR-ABL transcript levels monitored monthly until previous MMR or MR 4.0 level is re-established and every 12 weeks thereafter1,3

ENESTfreedom is a single-arm, phase II trial assessing the potential for treatment-free remission in 215 patients with Ph+ CML-CP following frontline nilotinib treatment. The primary efficacy endpoint was the proportion of patients who were in MMR without reinitiation of treatment at week 48 of the TFR phase.

ENESTop is a single-arm, phase II trial assessing treatment-free remission in 163 patients with Ph+ CML-CP who had switched from imatinib to nilotinib. The primary efficacy endpoint was the proportion of patients with successful TFR at 48 weeks, defined as no loss of MMR or confirmed loss of MR4 (2 consecutive RQ-PCR tests) within the first 48 weeks of TFR.

  1. TASIGNA® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; May 2017.
  2. Hochhaus A, et al. ENESTfreedom Study. Leukemia [published online March 17, 2017]. 2017:1-7. doi:10.1038/leu.2017.63.
  3. Hughes TP, et al. ENESTop Study. ASCO; June 3-7, 2016; Chicago, Illinois. Poster 7054.
  4. Rea D, et al. ENESTpath. ASH; December 4, 2016; San Diego, CA. Abstract 3094.
  5. Ritchie EK, et al. ENESTgoal. Blood. 2015;126:4050.