In an interview with PharmaShots, Mark Wildgust, VP of Global Medical Affairs, Oncology at Janssen, Dr. Paolo Ghia, Division of Experimental Oncology at Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele and Paul Barr, Associate Professor of Medicine and Director of the Clinical Trials Office for the Wilmot Cancer Institute at University of Rochester Medical Center share their views on the data of Amivantamab combo in NSCLC and Imbruvica in CLL presented at ASCO 2021.
- The CHRYSALIS study showed the effectiveness of Amivantamab + lazertinib for CT-naïve patients with EGFR exon 19 deletion or L858R mutations whose disease had progressed after treatment with Osimertinib
- First data from the FD cohort of the CAPTIVATE study demonstrated that FD Imbruvica + venetoclax can deliver an impact as a time-limited treatment option. 95% of patients treated with 12cycles of I+V as 1L therapy were alive and progression-free @2yrs. with deep remissions across all subgroups
- 7yrs. data from the RESONATE-2 study reinforce the survival benefits and long-term tolerability of Imbruvica in patients with CLL and RWE data support the use of Imbruvica as SOC
Response from Mark Wildgust, Vice President of Global Medical Affairs, Oncology at Janssen
Tuba: What is Janssen’s plan for ASCO’21 with its broader oncology portfolio?
- At ASCO & EHA, Janssen Oncology shared a combined total of nearly 50 company-sponsored presentations, including 13 oral presentations. At ASCO specifically, clinical data from more than 10 investigational and approved treatments for solid tumors and hematologic malignancies were presented.
- Highlights for Hematology include:
- Longer-term cilta-cel combined Phase 1b/2 data from CARTITUDE-1 study; first results from the Phase 2 CARTITUDE-2 study
- Updated data from the CHRYSALIS study show the effectiveness of amivantamab in combination with lazertinib for chemotherapy-naïve patients with epidermal growth factor receptor (EGFR) exon 19 deletion or L858R mutations whose disease had progressed after treatment with osimertinib
- Longer-term results from the pivotal Phase 1b/2 CARTITUDE-1 study in patients with heavily pre-treated disease and the first-ever results from the Phase 2 CARTITUDE-2 study in earlier lines of therapy, showing that a single infusion of cilta-cel led to early, deep and durable responses, and evidence that cilta-cel could potentially be transformative in terms of multiple myeloma patient outcomes.
- Updated results from the ongoing Phase 1 first-in-human dose escalation studies of teclistamab and talquetamab for the treatment of relapsed or refractory multiple myeloma
- First data from the CAPTIVATE study of IMBRUVICA-based combination as a fixed-duration therapy in previously untreated CLL
- At EHA, first data from the GLOW study of IMBRUVICA-based combination for previously untreated elderly or younger unfit patients with CLL was presented as a late-breaking abstract.
- Results from IMBRUVICA RESONATE-2 showing seven years of progression-free and overall survival data in First-Line Chronic Lymphocytic Leukemia (CLL)
- Updated results for DARZALEX FASPRO(daratumumab and hyaluronidase-fihj) in light chain (AL) amyloidosis and with DARZALEX(daratumumab) in newly diagnosed multiple myeloma
- At EHA, nearly five-year overall survival data in patients with newly diagnosed multiple myeloma from the MAIA study.
Highlights for Solid tumors include:
- Updated RYBREVANT (amivantamab-vmjw) and lazertinib data for the treatment for osimertinib-relapsed patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC)
- Long-term ERLEADA(apalutamide) patient reported outcomes data in metastatic castration-sensitive prostate cancer
- Outcomes for histology-agnostic patients receiving BALVERSA (erdafitinib) in the Phase 2 RAGNAR study
Tuba: What are the key highlights of the data of Imbruvica presented at ASCO?
- IMBRUVICA data being presented at this year’s ASCO further underscore the long-term benefit in chronic lymphocytic leukemia (CLL), as well as the commitment to meet the needs of patients and physicians with the potential of a fixed-duration combination for young, fit patients with CLL.
- First data from the fixed-duration cohort of the Phase 2 CAPTIVATE study support the potential for a fixed duration treatment approach in first-line treatment of CLL.
- Results from RESONATE-2 further underscore the long-term benefit of IMBRUVICA monotherapy in frontline CLL, adding to the growing breadth of data supporting IMBRUVICA as the only BTK inhibitor that has a demonstrated overall survival benefit and superior progression-free survival in first-line CLL over chemotherapy, helping patients live without progression of their cancer.
- IMBRUVICAdata was accepted as a late breaker at this year’s European Hematology Association (EHA) featuring the GLOW study, a Phase 3 trial for patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). GLOW is being featured as part of EHA’s press program.
Tuba: Are there any patient support programs, patient or HCP education programs for Imbruvica?
- We are listening and learning from people whose lives are touched by cancer, and we understand their treatment journeys and the support needed for patient care. Patients taking IMBRUVICA who are interested in an assistance program can visit IMBRUVICA By Your Side, which offers personalized support to help patients access and stay on track with IMBRUVICA. The program includes resources that help patients better understand and maintain their treatment, track their treatment and even connect them IMBRUVICA. By Your Side patient support Ambassadors.
- HCPs are encouraged to visit the IMBRUVICA HCP website for downloadable resources.
Tuba: What does Imbruvica mean to the company? How much it is helping the company to generate its revenue?
- IMBRUVICA is approved in more than 100 countries, and, to date, has been used to treat more than 230,000 patients worldwide. IMBRUVICA continues to demonstrate clinical benefits for patients and we are committed to exploring its full potential.
- Ibrutinib is a testimonial to the impact and focus Janssen has had on making a difference for patients with cancer, treating almost a quarter of a million patients worldwide and becoming a global standard of care for patients with CLL and other B-cell malignancies. Ibrutinib has set the standard for patients with CLL, no other targeted agents in CLL have the breadth of clinical benefit of ibrutinib and we are now moving into a position with 7-years of follow-up with RESONATE-2 and data on fixed duration of treatment that ibrutinib will be able to offer the ability for healthcare providers to tailor treatment to their patients goals and needs.
Tuba: Highlight Janssen’s efforts that enable the company to lead in oncology?
- As the fastest growing Oncology company, we are focused on transforming care and delivering innovative therapies for patients facing unmet medical needs to help them live longer and live better.
- We are reimagining how we connect and collaborate with healthcare professionals, patients, and caregivers—through care delivery, ingenuity, and by pushing boundaries.
- Our robust portfolio of cutting-edge oral, biologic, and cell therapies includes novel approaches to predict, prevent, intercept, detect and potentially defeat cancer—someday changing the way cancers are treated.
- At the congresses, Janssen showed that we are a leader in oncology with the 10 assets reviewed, ranging from multiple myeloma to prostate cancer. We have agents such as ibrutinib, daratumumab and apalutamide that are changing the standard of care, advancing new agents such as Amivantamab and cilta-cel to future innovations such as Teclistamab, Talquetamab, and TARIS-200.
Response from Dr. Paolo Ghia, MD, PhD, Division of Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele
Tuba: Discuss in detail about P-II CAPTIVATE study and its robust data?
- CAPTIVATE evaluated previously untreated patients with CLL who 70 years were or younger, including patients with high-risk disease.
- In the fixed-duration cohort (N=159; median age 60 years), patients received three cycles of ibrutinib lead-in therapy, followed by 12 cycles of combination ibrutinib plus venetoclax therapy, and then stopped therapy regardless of minimal residual disease (MRD) status. More than 90 percent of patients completed planned therapy of ibrutinib plus venetoclax treatment.
- At a median follow-up of 27.9 months, the overall response rate (ORR) was 96 percent and the complete response (CR) rate in the overall population was 56 percent (n=88; 95 percent Confidence Interval [CI]: 48–64) and was consistent across high-risk subgroups.
- Of the patients who achieved a CR, 89 percent had a durable CR of at least one year.
- Seventy-seven and 60 percent of patients achieved undetectable minimal residual disease (uMRD) at any time in the peripheral blood and bone marrow, respectively.
- Estimated 24-month progression-free survival (PFS) with ibrutinib plus venetoclax was 93 percent for patients with unmutated IGHV and 97 percent for patients with mutated IGHV (unmutated IGHV 95 percent CI: 85‒97; mutated IGHV 95 percent CI: 88‒99) and overall survival (OS) was 98 percent (95 percent CI: 94-99) for all treated patients.
Tuba: Unveil the potential of Imbruvica-based fixed-duration therapy in CLL & SLL?
- In the CAPTIVATE study, two well-established blood cancer treatments are combined to create a synergistic therapeutic regimen.
- The latest data from the CAPTIVATE study underscore that ibrutinib in combination with venetoclax, in an all-oral fixed duration, delivers a high rate of progression-free survival at two years while enabling treatment-free remission for patients.
- Though the use of continuous treatment with ibrutinib in CLL has been established as the standard of care for patients, including those with high-risk disease, fixed-duration therapy has been considered of potential value for patient treatment decreasing the time on the drug and the possibility of adverse events and likely preventing the occurrence of resistance to the therapy.
- Data from the CAPTIVATE study underscore that the combination of ibrutinib and venetoclax in an all-oral fixed duration combination also delivers a high rate of progression-free survival at two years while enabling treatment-free remission for patients.
Response from Paul Barr, MD, Associate Professor of Medicine and Director of the Clinical Trials Office for the Wilmot Cancer Institute at University of Rochester Medical Center
Tuba: What were the key points of the study to be noted from RESONATE-2?
- The results from RESONATE-2 further support the long-term efficacy of ibrutinib monotherapy in first-line chronic lymphocytic leukemia.
- RESONATE-2 evaluated 269 previously untreated patients with CLL aged 65 years or older, without del(17p) (a prognostic factor that tends to make patients harder to treat), who were randomly assigned to receive continuous ibrutinib or chlorambucil up to 12 cycles.
- With up to seven years of follow-up, PFS benefit with single-agent ibrutinib was sustained (PFS Hazard Ratio [HR] 0.160 [95 percent CI: 0.111–0.230]). At 6.5 years, the median PFS with ibrutinib had not been reached; 61 percent of patients treated with single-agent ibrutinib were alive and progression-free and nearly 1/2 of patients remain on ibrutinib.2
- The PFS benefit for patients treated with ibrutinib was seen in all subgroups, including those with high-risk genomic features of TP53 mutation, unmutated IGHV or 11q deletion (HR 0.091 [95 percent CI: 0.054–0.152]).
- Additionally, 78 percent of patients in the ibrutinib treatment-arm were alive at 6.5 years. The CR rate with ibrutinib treatment has increased over time to 34 percent.
Main Image Source: Cancer Therapy Advisor
About Mark Wildgust:
Mark Wildgust is the Vice President of Global Medical Affairs, Oncology at Janssen.
About Dr. Paolo Ghia:
Dr. Paolo Ghia is the Professor at Division of Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele.
About Paul Barr:
Paul Barr is the Associate Professor of Medicine and Director of the Clinical Trials Office for the Wilmot Cancer Institute at the University of Rochester Medical Center.