New Data Presented at ASH from the Phase 3 GLOW Study Show Fixed-Duration, First-Line Treatment with IMBRUVICA® (ibrutinib) Plus Venetoclax Demonstrated an Overall Survival Rate of More Than 84 Percent at 54 Months in Patients with Chronic Lymphocytic Leukaemia

New Data Presented at ASH from the Phase 3 GLOW Study Show Fixed-Duration, First-Line Treatment with IMBRUVICA® (ibrutinib) Plus Venetoclax Demonstrated an Overall Survival Rate of More Than 84 Percent at 54 Months in Patients with Chronic Lymphocytic Leukaemia

Additional data from the Phase 2 CAPTIVATE study, show 82 percent of patients with previously untreated chronic lymphocytic leukaemia (CLL) treated with fixed-duration ibrutinib plus venetoclax did not need next-line treatment at 54 months^1,2

BEERSE, BELGIUM, Dec. 11, 2023 (GLOBE NEWSWIRE) -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new long-term follow-up data at the 2023 American Society of Hematology (ASH) Annual Meeting, from the Phase 3 GLOW (Abstract #634) and Phase 2 CAPTIVATE studies (Abstract #633) evaluating first-line, fixed-duration treatment with IMBRUVICA^® (ibrutinib) plus venetoclax (I+V) – both featured as oral presentations at the Congress, taking place in San Diego from 9-12 December.^1,2 The GLOW study demonstrated an estimated 84.5 percent overall survival (OS) rate at 54 months, among older and/or comorbid patients with previously untreated CLL treated with I+V, compared to 63.7 percent for patients treated with chlorambucil plus obinutuzumab (Clb+O).¹

Phase 2 results from the CAPTIVATE study, which utilised a similar I+V regimen as the GLOW study, showed deep remissions with clinical meaningful progression-free survival (PFS) with the I+V combination.² In the I+V fixed-duration (FD) cohort, rates of PFS remained high and durable, with 70 percent (95 percent Confidence Interval [CI], 62-77) of patients treated with I+V alive and without disease progression after 54 months.² 

“We are incredibly proud of the impact ibrutinib continues to have in improving outcomes and experiences for patients living with CLL,” said Edmond Chan, MBChB, M.D. (Res), Senior Director, EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. “It is the only targeted therapy to demonstrate a significant overall survival benefit in randomised Phase 3 studies in this first-line setting, and the latest updates presented at ASH 2023 show that with longer follow-up, this fixed-duration ibrutinib-based combination regimen maintains deep and durable responses, including in higher-risk patients.”

Data on Survival Benefits and Time to Next Treatment for First-Line, Fixed-Duration Treatment with Ibrutinib Plus Venetoclax At Median 57-Month Follow-Up from the GLOW Study

In the GLOW study, patients with CLL aged ≥65 years or 18 to 64 years who also had a cumulative illness rating scale (CIRS) score higher than six or creatine clearance of less than 70 mL/min were randomised to I+V (n=106) or Clb+O (n=105).¹

“Results from the five-year update of the GLOW study continue to demonstrate the sustained efficacy of fixed-duration I+V in older patients and those with comorbidities with previously untreated CLL,” said George Follows, PhD, Consultant Hematologist at Cambridge University Addenbrooks Hospital & Clinical Lead for Lymphoma/CLL.* “While there is currently no cure for CLL, it’s very promising to see the consistent efficacy and durable responses from almost five years of follow-up.”

Phase 3 GLOW Study Results

• With a median follow-up of 57.3 months (range, 1.7-65.2), the primary endpoint of PFS remained superior for I+V versus Clb+O (HR 0.256 [95% CI, 0.172-0.382]).¹
• Estimated PFS rates at 54 months were 66.5 percent in I+V-treated patients compared to 19.5 percent for those treated with Clb+O.¹
• Patients treated with I+V continued to have an OS advantage, reducing the risk of death by 55 percent (HR 0.453 [95 percent CI, 0.261-0.785]; p=0.0038).¹ Estimated 54-month OS rates were 84.5 percent in the I+V arm compared to 63.7 percent of patients in the control arm treated with Clb+O.¹
• The risk of needing second-line therapy was significantly reduced by 82 percent with first-line I+V versus Clb+O (HR 0.185 [95 percent CI, 0.096-0.355]; p<0.0001).¹
• At 54 months, 87.9 percent of patients treated with I+V did not require subsequent therapy.¹
• I+V resulted in PFS rates at 54 months for patients with unmutated immunoglobulin heavy-chain variable region gene (uIGHV; n=67) and mutated immunoglobulin heavy-chain variable region gene (mIGHV; n=32) of 59 percent and 90 percent, respectively.¹
• In patients with mIGHV, PFS rates at 42 months post- I+V treatment were greater than or equal to 91 percent, regardless of minimal residual disease (MRD) status at three months after end of treatment (EOT+3).¹
• In patients with uIGHV, PFS rates at three years post- I+V treatment were 81 percent for patients achieving uMRD at EOT+3.^1,3
• Thirty-eight months after the end of I+V treatment, 32.1 percent of patients had undetectable MRD (uMRD).¹ Of the patients who achieved uMRD three months after I+V treatment (n=58), 53.4 percent sustained uMRD status 38 months following treatment.^1,3
• Results from the four-year follow-up study were recently published in The Lancet Oncology, on 6 November, 2023.

Data on Retreatment with Single-Agent Ibrutinib in the Phase 2 CAPTIVATE Study (PCYC-1142)
Phase 2 results from the FD cohort of the CAPTIVATE study, which utilised a similar I+V regimen as the GLOW study in patients with CLL up to 70 years of age, showed deep remissions and clinically meaningful PFS with the I+V combination. Additionally, patients with MRD were evaluated.² 

Phase 2 CAPTIVATE Study Results

• At nearly five years, 82 percent of patients experienced freedom from next-line CLL treatment (95 percent CI, 76–87).²
• Of the 202 patients treated with I+V in either the FD cohort (n=159) or the MRD cohort (n=43), 53 patients have had progressive disease (PD) to date with the majority occurring after two years of completing treatment.²
• Twenty-two of these patients have initiated retreatment with single-agent ibrutinib.² With a median follow-up of 17 months (range, 0–45), overall response rate (ORR) in 21 response-evaluable patients was 86 percent, with best response of complete response (CR) (n=1 [5 percent]), partial response (PR; n=17 [81 percent]), PR with lymphocytosis (n=1 [5 percent]), stable disease (n=1 [5 percent]), and PD (n=1 [5 percent]).^2,4
• Among these patients there were no ibrutinib dose reductions or discontinuations due to adverse events (AEs) in those retreated with single agent ibrutinib.²
• In the FD cohort, the 54-month PFS and OS rates were 70 percent (95 percent CI, 62-77) and 97 percent (95 percent CI, 93-99), respectively.²

Updated data for both studies showed the safety profile of the I+V regimen was consistent with known safety profiles of ibrutinib and venetoclax.² Safety was not further assessed in the GLOW study as all patients were already past the treatment-emergent period in previous analyses.¹ Safety analysis was limited to the incidence of second primary malignancies.¹ In the CAPTIVATE study, serious AEs considered related to study treatment and second malignancies continued to be collected after completion of fixed-duration treatment.² In total, second primary malignancies occurred in eight percent of patients and one AE of basal cell carcinoma occurred during this additional year of follow-up.²

“GLOW and CAPTIVATE are the longest fixed-duration I+V studies in patients living with CLL with nearly five years of results," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Johnson & Johnson Innovative Medicine. “Together, the consistency of data from these studies elevate I+V as a first-line, all oral therapy and further demonstrate the long-term scientific innovation of ibrutinib in changing the standard of care for patients living with CLL and other B-cell malignancies.”