New IMBRUVICA® (ibrutinib) Data in Fixed-Duration Combination Regimen Presented at EHA 2022 Shows Deep, Durable Response at Three Years in Untreated Chronic Lymphocytic Leukemia



New IMBRUVICA® (ibrutinib) Data in Fixed-Duration Combination Regimen Presented at EHA 2022 Shows Deep, Durable Response at Three Years in Untreated Chronic Lymphocytic Leukemia

The all-oral, as soon as-each day mixture routine also demonstrates the capability of immune recuperation on this patient populace

VIENNA, June 10, 2022 /PRNewswire/ — The Janssen Pharmaceutical Companies of Johnson & Johnson these days introduced new and updated outcomes from the Phase 2 CAPTIVATE look at evaluating IMBRUVICA^® (ibrutinib) in mixture with venetoclax (I+V) as a capability constant-period (FD) remedy in adult sufferers with formerly untreated persistent lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Updated information from the FD cohort with 3 years of observe-up shows that I+V keeps to illustrate deep and sturdy responses and clinically meaningful progression-unfastened survival (PFS) and basic survival (OS) in the first-line treatment placing. New statistics may be offered from the minimum residual ailment (MRD) cohort, which shows immune recovery with this combination. These statistics could be provided all through the 2022 European Hematology Association (EHA) Annual Congress taking area in Vienna, Austria June nine-12 (Abstracts #S144 and #P669). 

“These promising information spotlight the complementary mechanism of action among ibrutinib and venetoclax in a hard and fast-duration aggregate regimen,” said Carol Moreno, M.D., Ph.D., Consultant Hematologist, Hospital de los angeles Santa Creu Sant Pau, Autonomous University of Barcelona, Barcelona, Spain, and examine investigator.^† “The CAPTIVATE have a look at suggests that this mixture may also have the ability to offer remedy-free remissions for sufferers and efficiently get rid of CLL cells and help to repair ordinary B cells to healthy donor stages in sufferers with formerly untreated CLL/SLL.”

The Phase 2 CAPTIVATE (PCYC-1142) study (NCT02910583) – sponsored by means of Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc. – enrolled 323 patients with formerly untreated CLL/SLL who were younger than 70 years, including sufferers with high-danger sickness, in cohorts: an FD cohort wherein all patients stopped remedy after 12 cycles of the aggregate, no matter MRD popularity; and an MRD-guided cohort where remedy duration became guided via the sufferers’ MRD fame after 12 cycles of I+V mixture (patients who met criteria for showed undetectable minimal residual disease [uMRD] were randomized 1:1 to placebo or IMBRUVICA^®; patients who did no longer meet uMRD criteria have been randomized to IMBRUVICA^® or I+V).^1,2 

Three-Year Follow-Up Data from the FD Cohort of the Phase 2 CAPTIVATE (PCYC-1142) Study of IMBRUVICA^®-Based Combination Regimen in Previously Untreated Patients with CLL/SLL (Abstract #P669)¹

After an additional 12 months of follow-up statistics from the FD cohort of CAPTIVATE, I+V maintains to demonstrate deep, durable responses and clinically meaningful PFS, which include in patients with del(17p)/TP53 mutated or unmutated immunoglobulin heavy chain gene (IGHV).¹ The scientific facts underscore the distinct and complementary modes of action of IMBRUVICA^® and venetoclax (a BCL-2 inhibitor).¹ IMBRUVICA^® has been shown to mobilize CLL cells out of lymph nodes and different lymphoid niches and into peripheral blood where they’re extra vulnerable to venetoclax-precipitated apoptosis, removing dividing and resting CLL cells.¹

Key findings from the Phase 2 CAPTIVATE FD cohort examine consist of:

• At an average comply with-up of 38.7 months, the 36-month PFS rate was 88 percent for all dealt with patients, eighty percent for sufferers with del(17p)/TP53 mutated and 86 percent for unmutated IGHV sufferers (ninety five percent Confidence Interval [CI]).¹
• With an additional year of follow-up, no extra OS activities befell. The 36-month OS charge was ninety eight percent, average (ninety five percentage CI).¹
  • The 36-month OS charges had been similar in sufferers with del(17p)/TP53 mutated (96 percentage) or unmutated IGHV (ninety seven percentage).¹
• The entire reaction (CR) fee became 57 percentage (n=159; 95 percentage CI, 50-sixty five) and steady throughout excessive-risk subgroups.¹
• Median length of CR turned into now not reached (n=ninety one); the 24-month landmark estimate for length of CR turned into 94 percent. Median duration of reaction was not reached for responding patients (n=153).¹
• Seventy-9 percentage of sufferers (n=one hundred twenty five) achieved undetectable uMRD at any time within the peripheral blood (PB) and/or bone marrow.¹
• Of patients with uMRD in PB at 3 months posttreatment, 78 percent (66/eighty five) of evaluable patients maintained uMRD thru 12 months posttreatment.¹
• All sufferers are currently off treatment.¹ Frequently happening treatment-emergent adverse activities (TEAEs) (period from first dose till 30 days after the final dose of observe remedy) were in most cases Grade half of in severity excluding neutropenia.¹ Median time to onset of regularly occurring TEAEs usually took place inside 4 months (87-one hundred percentage).¹ The median time to decision or development ranged from 16.5 days (diarrhea) to 42.5 days (arthralgia).¹ No new severe unfavourable occasions or secondary malignancies have been mentioned because the primary evaluation.¹
• Twelve sufferers who advanced after FD treatment with I+V had been retreated with single-agent IMBRUVICA^®; 11 of the 12 patients were evaluable for response, with 10 responding.¹

New Data from the MRD-Guided Cohort of the Phase 2 CAPTIVATE (PCYC-1142) Study of IMBRUVICA^®-Based Combination Regimen Evaluating Immune Restoration in Previously Untreated Patients with CLL/SLL (Abstract #S144)²

Data at the adjustments over time within the mobile immune profile in patients with CLL/SLL dealt with with the I+V combination and age-matched healthy donors have been featured in an oral presentation at EHA. The FD regimen of I+V inside the confirmed uMRD placebo arm correctly eliminated CLL cells to healthy donor levels and enabled sustained regeneration of normal B cellular counts.² 

Immune recovery was evaluated in seventy nine previously untreated patients with CLL/SLL enrolled within the MRD cohort by means of monitoring adjustments over time in the cell immune profile of sufferers handled with I+V aggregate routine and in comparison to twenty age-matched healthful donors.² 

Key findings from this evaluation include:

• Patients with showed uMRD (n=40) had a considerably more reported lower in circulating CLL cellular be counted than sufferers with uMRD not showed (n=39).² 
  • At Cycles seven and sixteen the p-value changed into <zero.0001 with I+V mixture remedy.² 
• From Cycle sixteen – 29, sufferers with Confirmed uMRD (n=40) had cell counts much like the ones of wholesome donors (≤0.Eight cellular/μL).²
• Normalization of essential immune cells, such as T-cell subsets, classical monocytes, and dendritic cellular counts was discovered in this population.² 

“These new scientific and immune results from the CAPTIVATE observe add similarly proof of the promise of IMBRUVICA in a hard and fast-duration regimen for formerly untreated CLL patients,” stated Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. “IMBRUVICA has grow to be a standard of care in CLL remedy, and we retain to explore novel mixtures including I+V which might also offer the option of off-remedy, disease-unfastened intervals for patients with B-cell malignancies.”

The CAPTIVATE have a look at is a part of a complete improvement application exploring the potential of IMBRUVICA^®-based totally FD therapy. Janssen keeps to assess the I+V combination regimen and its capability to offer a FD remedy option for patients dwelling with CLL/SLL. Recently, The New England Journal of Medicine Evidence posted the primary analysis from the Phase 3 GLOW have a look at, which evaluated the protection and efficacy of the I+V aggregate in older or not worthy sufferers with CLL/SLL, and confirmed that the combination validated advanced PFS and deeper sustained responses as compared to chemoimmunotherapy in first-line CLL.³

About IMBRUVICA^®

IMB­RUVICA^® (ibrutinib) is a as soon as-every day oral medicine this is together evolved and commercialized by way of Janssen Biotech, Inc. And Pharmacyclics LLC, an AbbVie business enterprise. IMBRUVICA^® blocks the Bruton’s tyrosine kinase (BTK) protein, which is wanted by way of everyday and strange B cells, consisting of unique cancer cells, to multiply and unfold. By blocking BTK, IMBRUVICA^® may also help flow extraordinary B cells out in their nourishing environments and inhibits their proliferation.^four,five,6

IMBRUVICA^® is accepted in greater than one hundred nations and has been used to treat extra than 250,000 patients international. There are extra than 50 enterprise-backed scientific trials, inclusive of 18 Phase 3 research, over eleven years comparing the efficacy and safety of IMBRUVICA^®.

IMBRUVICA^® was first permitted by means of the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult sufferers in six ailment areas, together with five hematologic cancers. These consist of symptoms to deal with adults with CLL/SLL with or without 17p deletion (del17p), and adults with Waldenström’s macroglobulinemia (WM), and adult patients with formerly handled mantle cellular lymphoma (MCL)*, in addition to to treat person sufferers with previously handled marginal area lymphoma (MZL) who require systemic therapy and have received at the least one earlier anti-CD20-based totally remedy*, and person patients with previously handled persistent graft-versus-host disorder (cGVHD) after failure of one or more strains of systemic therapy.⁷

*Accelerated approval become granted for MCL and MZL primarily based on universal response price. Continued approval for MCL and MZL can be contingent upon verification and outline of scientific gain in confirmatory trials.

Since 2019, the National Comprehensive Cancer Network^® (NCCN^®), recommends ibrutinib (IMBRUVICA^®) as a desired regimen for the preliminary treatment of CLL/SLL and has Category 1 treatment status for remedy-naïve sufferers without deletion 17p/TP53 mutation and as a desired remedy for remedy-naïve patients with deletion 17p/TP53 mutation. The NCCN Guidelines^® additionally suggest IMBRUVICA^®, with or without rituximab, as a desired regimen for the treatment of relapsed/refractory MCL, as a Category 1 preferred regimen for each untreated and previously handled WM patients, and as a favored routine for relapsed/refractory MZL.^eight

For greater facts, go to www.IMBRUVICA.Com.

IMBRUVICA^® IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding occasions have took place in patients who acquired IMBRUVICA^®. Major hemorrhage (≥ Grade 3, serious, or any primary apprehensive gadget events; e.G., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) came about in 4.2% of patients, with fatalities taking place in zero.4% of 2,838 sufferers who obtained IMBRUVICA^® in 27 scientific trials. Bleeding activities of any grade such as bruising and petechiae took place in 39%, and aside from bruising and petechiae took place in 23% of sufferers who received IMBRUVICA^®, respectively.

The mechanism for the bleeding activities isn’t always nicely understood.

Use of both anticoagulant or antiplatelet dealers concomitantly with IMBRUVICA^® will increase the risk of principal hemorrhage. Across medical trials, three.1% of 2,838 sufferers who obtained IMBRUVICA^® without antiplatelet or anticoagulant remedy experienced primary hemorrhage. The addition of antiplatelet therapy with or without anticoagulant remedy expanded this percentage to 4.4%, and the addition of anticoagulant therapy without or with antiplatelet therapy increased this percent to 6.1%. Consider the risks and advantages of anticoagulant or antiplatelet therapy while co-administered with IMBRUVICA^®. Monitor for signs and symptoms of bleeding.

Consider the gain-hazard of withholding IMBRUVICA^® for as a minimum 3 to 7 days pre- and post-surgical treatment relying upon the form of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (inclusive of bacterial, viral, or fungal) have passed off with IMBRUVICA^® remedy. Grade three or greater infections came about in 21% of one,476 patients who acquired IMBRUVICA^® in clinical trials. Cases of revolutionary multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have took place in sufferers dealt with with IMBRUVICA^®. Consider prophylaxis according to traditional of care in patients who’re at elevated chance for opportunistic infections. Monitor and evaluate sufferers for fever and infections and deal with correctly.

Cardiac Arrhythmias, Cardiac Failure and Sudden Death: Fatal and critical cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA^®. Deaths due to cardiac causes or surprising deaths came about in 1% of 4,896 sufferers who acquired IMBRUVICA^® in scientific trials, consisting of in patients who obtained IMBRUVICA^® in unapproved monotherapy or combination regimens. These detrimental reactions passed off in sufferers with and with out preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities can be at extra hazard of those activities.

Grade three or extra ventricular tachyarrhythmias had been reported in 0.2%, Grade 3 or greater atrial traumatic inflammation and atrial flutter were reported in 3.7%, and Grade three or extra cardiac failure became said in 1.Three% of 4,896 patients who acquired IMBRUVICA^® in scientific trials, inclusive of in sufferers who acquired IMBRUVICA^® in unapproved monotherapy or combination regimens. These activities have passed off especially in patients with cardiac danger factors such as hypertension and diabetes mellitus, a previous records of cardiac arrhythmias, and in sufferers with acute infections.

Evaluate cardiac records and characteristic at baseline, and display sufferers for cardiac arrhythmias and cardiac characteristic. Obtain similarly evaluation (e.G., ECG, echocardiogram) as indicated for patients who expand symptoms of arrhythmia (e.G., palpitations, lightheadedness, syncope, chest ache), new onset dyspnea, or different cardiovascular worries. Manage cardiac arrhythmias and cardiac failure correctly, comply with dose modification guidelines, and recall the dangers and advantages of persisted IMBRUVICA^® remedy.

Hypertension: Hypertension passed off in 19% of 1,476 patients who received IMBRUVICA^® in scientific trials. Grade 3 or extra hypertension passed off in 8% of patients. Based on records from 1,124 of these sufferers, the median time to onset become five.Nine months (range, 0.03 to 24 months). Monitor blood pressure in patients treated with IMBRUVICA^®, initiate or modify anti-hypertensive medicinal drug throughout remedy with IMBRUVICA^® as suitable, and observe dosage modification tips for Grade three or higher high blood pressure.

Cytopenias: In 645 patients with B-cell malignancies who acquired IMBRUVICA^® as a unmarried agent, grade 3 or four neutropenia befell in 23% of sufferers, grade 3 or four thrombocytopenia in eight% and grade 3 or 4 anemia in 2.Eight%, based on laboratory measurements. Monitor entire blood counts monthly.

Second Primary Malignancies: Other malignancies (10%), which includes non-skin carcinomas (three.Nine%), occurred some of the 1,476 patients who obtained IMBRUVICA^® in scientific trials. The maximum common 2d number one malignancy became non-cancer skin most cancers (6%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been every so often reported with IMBRUVICA^®. Assess the baseline chance (e.G., high tumor burden) and take appropriate precautions. Monitor patients carefully and deal with as suitable.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA^® can reason fetal harm whilst administered to a pregnant female. Advise pregnant girls of the potential danger to a fetus. Advise women of reproductive ability to apply effective birth control during treatment with IMBRUVICA^® and for 1 month after the final dose. Advise men with woman partners of reproductive ability to use effective birth control at some point of the equal term.

ADVERSE REACTIONS

B-cell malignancies: The maximum commonplace unfavorable reactions (≥30%) in sufferers with B-cellular malignancies (MCL, CLL/SLL, WM and MZL) have been thrombocytopenia (54.5%)*, diarrhea (forty three.Eight%), fatigue (39.1%), musculoskeletal ache (38.Eight%), neutropenia (38.6%)*, rash (35.Eight%), anemia (35.0%)*, and bruising (32.Zero%).

The most commonplace Grade ≥ 3 damaging reactions (≥five%) in patients with B-cellular malignancies (MCL, CLL/SLL, WM and MZL) had been neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%), and high blood pressure (eight.Zero%).

Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of sufferers had a dose reduction because of unfavorable reactions. Approximately 4-10% (CLL/SLL), nine% (MCL), and 7% (WM [5%] and MZL [13%]) of sufferers discontinued because of detrimental reactions. 

cGVHD: The maximum not unusual detrimental reactions (≥20%) in patients with cGVHD have been fatigue (57%), bruising (forty%), diarrhea (36%), thrombocytopenia (33%)*, muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade three or higher detrimental reactions (≥5%) stated in patients with cGVHD were pneumonia (14%), fatigue (12%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), hypokalemia (7%), headache (five%), musculoskeletal pain (five%), and pyrexia (five%).

Twenty-four percentage of patients receiving IMBRUVICA^® inside the cGVHD trial discontinued treatment because of destructive reactions. Adverse reactions leading to dose reduction took place in 26% of sufferers.

*Treatment-emergent decreases (all grades) were based on laboratory measurements.

DRUG INTERACTIONS

CYP3A Inhibitors: Co-administration of IMBRUVICA^® with sturdy or mild CYP3A inhibitors can also increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may also growth the threat of drug-related toxicity. Dose adjustments of IMBRUVICA^® are encouraged when used concomitantly with posaconazole, voriconazole, and mild CYP3A inhibitors. Avoid concomitant use of different sturdy CYP3A inhibitors. Interrupt IMBRUVICA^® if robust inhibitors are used brief-time period (e.G., for ≤ 7 days). Avoid grapefruit and Seville oranges all through IMBRUVICA^® remedy, as those comprise sturdy or slight inhibitors of CYP3A. See dose change suggestions in USPI sections 2.3 and 7.1. 

CYP3A Inducers: Avoid coadministration with sturdy CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA^® in patients with severe hepatic impairment. In sufferers with moderate or slight impairment, lessen recommended IMBRUVICA^® dose and reveal greater frequently for detrimental reactions of IMBRUVICA^®.

Please click on right here to peer the entire Prescribing Information.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re developing a destiny wherein sickness is a component of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, operating tirelessly to make that destiny a truth for sufferers everywhere by means of combating illness with technology, improving get entry to with ingenuity, and recovery hopelessness with coronary heart. We recognition on regions of medication wherein we are able to make the largest distinction: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn extra at www.Janssen.Com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. Are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

^†Dr. Moreno has served as a paid representative to Janssen; she has now not been paid for any media paintings.

Cautions Concerning Forward-Looking Statements

This press launch contains “forward-looking statements” as described inside the Private Securities Litigation Reform Act of 1995 concerning product improvement and the potential advantages and treatment effect of IMBRUVICA^® (ibrutinib). The reader is suggested no longer to depend on these ahead-looking statements. These statements are based on current expectations of future activities. If underlying assumptions show inaccurate or acknowledged or unknown dangers or uncertainties materialize, real outcomes should vary materially from the expectancies and projections of Janssen Research & Development, LLC or any of the opposite Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but aren’t restrained to: demanding situations and uncertainties inherent in product studies and development, consisting of the uncertainty of medical fulfillment and of obtaining regulatory approvals; uncertainty of industrial fulfillment; production difficulties and delays; competition, along with technological advances, new merchandise and patents attained with the aid of competition; challenges to patents; product efficacy or protection concerns resulting in product recalls or regulatory action; adjustments in conduct and spending patterns of clients of fitness care services and products; modifications to relevant legal guidelines and rules, together with international fitness care reforms; and tendencies toward fitness care cost containment. A similarly listing and outlines of these dangers, uncertainties and different factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the financial 12 months ended January 2, 2022, consisting of inside the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s next Quarterly Reports on Form 10-Q and different filings with the Securities and Exchange Commission. Copies of these filings are to be had on-line at www.Sec.Gov, www.Jnj.Com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to replace any forward-searching declaration as a result of recent data or destiny events or traits.

¹ Moreno C., et al. Fixed-Duration Ibrutinib + Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: three-Year Follow-Up From the FD Cohort of the Phase 2 CAPTIVATE Study. 2022 European Hematology Association Annual Congress. June nine-12, 2022.

² Soloman I., et al. Immune Restoration and Synergistic Activity With First-Line Ibrutinib Plus Venetoclax: Translational Analyses of CAPTIVATE Patients with CLL. 2022 European Hematology Association Annual Congress. June nine-12, 2022.

³ Kater, A., et al. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evidence. 2022. Accessed June 2022 https://doi.Org/10.1056/evidoa2200006

⁴ Genetics Home Reference. Isolated boom hormone deficiency. http://ghr.Nlm.Nih.Gov/condition/remoted-boom-hormone-deficiency. Accessed June 2022.

^five Turetsky A, et al. Single cell imaging of Bruton’s tyrosine kinase using an irreversible inhibitor. Scientific Reports. 2014;6:4782.

⁶ de Rooij MF, Kuil A, Geest CR, et al. The clinically energetic BTK inhibitor PCI-32765 objectives B-mobile receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594.

⁷ IMBRUVICA^® U.S. Prescribing Information, May 2022.

⁸ NCCN^® Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V2.2022. National Comprehensive Cancer Network. Accessed June 2022.

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