Shots:
- Recently, at ASH 2024, Takeda presented data from several ongoing clinical trials across hematology and oncology, including the Phase II OPTIC and Phase III PhALLCON studies, among others
- Phuong Khanh Morrow, Head of the Oncology Therapeutic Area Unit at Takeda, shed light on Takeda’s key presentations at ASH 2024
- Phuong also highlighted the findings from the Phase III HD21 study, which demonstrated promising efficacy and safety outcomes in the treatment of lymphoma.
Saurabh: How has ICLUSIG improved the standard of care for the treatment for Ph+ ALL patients?
Phuong: ICLUSIG, when combined with chemotherapy is the first and only targeted treatment approved in the U.S. for adults with newly diagnosed Ph+ ALL, a historically difficult-to-treat cancer. Ph+ ALL is an extremely aggressive cancer that can lead to poor clinical outcomes. In some cases, people with newly diagnosed Ph+ ALL demonstrate poor molecular response rates or develop mutations that are resistant to first- and second-generation tyrosine kinase inhibitors (TKIs). There has long been a need for a potent TKI that can suppress mutation development and elicit deep responses in the frontline. ICLUSIG may help address these factors and impact long-term outcomes.
Saurabh: Are there any new findings discovered on safety and efficacy during the 5-year follow-up study of the P-II OPTIC study?
Phuong: In addition to providing long-term efficacy data and manageable safety data in a highly resistant chronic-phase (CP) CML population that are consistent with previous results, an exploratory, post-hoc analysis of the end of treatment (EOT) BCR::ABL1 mutational landscape was conducted. This is the first time EOT mutational results have been available from this study.
Data from the EOT analysis showed that among those with no baseline mutations and available EOT data, BCR::ABL1 mutations were detected in six patients. In addition, some who enrolled in OPTIC with existing BCR::ABL1 mutations had fewer or undetectable mutations at EOT. Overall, it is estimated that approximately 20-30% of patients with CML will experience treatment resistance to certain TKIs, largely caused by BCR::ABL1 mutations. Given this high rate of treatment resistance, suppressing mutations at the earliest possible line of therapy is vital for patients with CML to achieve long-term outcomes. This data supports ICLUSIG’s potential ability to suppress emerging mutations and reduce mutational burden in the BCR::ABL1 oncoprotein at the approved 45-mg starting dose.
Saurabh: What were the objectives of the two post-hoc analyses conducted for the P-III PhALLCON trial? Can you walk us through the findings?
Phuong: A post-hoc subgroup analysis was conducted to investigate the effect of ICLUSIG or imatinib as a single agent therapy following 20 cycles of the chemotherapy combination. The analysis found that patients treated with ICLUSIG maintained durable measurable residual disease (MRD)-negativity (95% and 67%, respectively) and comparable safety to imatinib treatment-emergent adverse event (TEAE) rates post cycle at 12 and 14% respectively). While ICLUSIG as single agent after chemotherapy for newly diagnosed Ph+ ALL is not an approved regimen, the results of this post-hoc analysis provide a better understanding of ICLUSIG as a monotherapy after 20 cycles of ICLUSIG in combination with chemotherapy in patients with newly diagnosed Ph+ ALL.
Another post-hoc analysis was conducted to compare quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) from ICLUSIG vs. imatinib administered in combination with reduced-intensity chemotherapy in patients with newly diagnosed Ph+ ALL. This analysis showed that treatment with ICLUSIG resulted in significantly and meaningfully longer quality-adjusted survival compared to imatinib. Ultimately, results from this study demonstrate ICLUSIG’s potential ability to help sustain patients’ quality of life longer than imatinib, further strengthening the clinical benefit:risk profile of ICLUSIG for adults with newly diagnosed Ph+ ALL.
ADCETRIS HD21
Saurabh: Can you share the findings of the Phase III HD21 study?
Phuong: Four presentations evaluating data from the Phase 3 HD21 study will be featured at ASH 2024, including:
- The German Hodgkin Study Group’s (GHSG) oral presentation from the Phase 2 single-arm elderly cohort of the HD21 trial, which demonstrated that PET-guided ADCETRIS in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) is feasible and tolerable, with appropriate dose adjustments and close monitoring, in elderly patients.
After a median follow-up of 23 months, 87% of patients treated with BrECADD achieved complete response (CR) and 12% were in partial remission. Corresponding 1-year and 2-year overall survival (OS) rates were 96.2% and 90.7%, respectively; progression-free survival (PFS) estimates at 1 year and 2 years were 95.1% and 91.5%, consistent with 2-year PFS rates observed in younger patients. Overall, 45% of patients experienced neutropenic fever and the treatment-related morbidity (TRMB) rate was 77%. No death was attributed to study treatment. Eleven second primary malignancies were reported during follow-up, most of which were other lymphomas.
- A post-hoc analysis evaluating the impact of impact of TRMB on health-related quality of life (HRQoL) in patients with advanced stage Hodgkin lymphoma receiving multiagent therapy, suggests that fewer TRMB events can improve patient experience, providing validation for TRMB during treatment period as a clinically meaningful and patient-relevant endpoint in the HD21 trial.
- A targeted literature review applying an algorithm to estimate utility values for the HD21 trial showed that completing chemotherapy improved utility in the progression-free state, indicating that BrECADD’s PFS improvement could increase quality-adjusted survival for adults with advanced-stage Hodgkin lymphoma.
- A post-hoc analysis evaluating chemotherapy-induced peripheral neuropathy (CIPN) sensory symptoms demonstrated that patients with these symptoms reported poorer overall health and more fatigue, suggesting that treatments with fewer CIPN symptoms may prevent a detrimental impact patients’ HRQoL.
Image Source: Canva
About the Author:
PK Morrow
PK Morrow, MD, is Head of the Oncology Therapeutic Area Unit at Takeda. She joined the company in January of 2024 and is responsible for Takeda’s oncology R&D strategy and development portfolio.
Prior to joining Takeda, Dr. Morrow served as Chief Medical Officer at CRISPR Therapeutics and spent over a decade at Amgen overseeing end-to-end development of clinical programs spanning hematology, oncology, diabetes and cardiovascular disease states. Before joining the industry, she held the role of Assistant Professor, Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center, where she co-led the development of the first multidisciplinary breast cancer survivorship clinic and served as the principal investigator of multiple drug studies.
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