Rigel Pharmaceuticals Unveils Promising Final Data from GAVRETO and REZLIDHIA Clinical Trials at ASCO and EHA 2025
Key Insights
Final data from the Phase 1/2 ARROW study demonstrates GAVRETO's durable efficacy in RET (search) fusion-positive NSCLC (search), with a 70.3% overall response rate and median overall survival of 44.3 months.
GAVRETO shows promising anti-tumor activity in various RET (search) fusion-positive solid tumors beyond lung cancer, including a 100% response rate in pancreatic cancer (search) patients.
REZLIDHIA data supports its potential clinical benefit when used in earlier treatment lines for relapsed/refractory AML (search) patients and as maintenance therapy, with particularly strong outcomes in patients with fewer prior therapies.
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) has announced seven upcoming poster presentations at two major oncology conferences, showcasing final data from clinical trials of its cancer therapies GAVRETO® (pralsetinib) and REZLIDHIA® (olutasidenib). The presentations will take place at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 30 to June 3, and the European Hematology Association (EHA) 2025 Congress in Milan from June 12 to June 15.
GAVRETO Shows Durable Responses in RET Fusion-Positive NSCLC
Final data from the Phase 1/2 ARROW study demonstrates GAVRETO's significant efficacy in patients with RET (search) fusion-positive non-small cell lung cancer (search) (NSCLC (search)). The results show an overall response rate (ORR) of 70.3% and a median duration of response (DOR) of 19.1 months in the measurable disease population (n=259).
In the efficacy population (n=281), median overall survival (OS) reached 44.3 months with a median follow-up of 47.6 months. Notably, median progression-free survival (PFS) was 13.1 months overall but showed geographic variations, with significantly longer PFS in the United States (25.9 months) compared to Asia (12.6 months) or Europe (12.9 months).
"The study data continue to demonstrate GAVRETO's clinically meaningful and durable responses in patients with RET (search) fusion-positive NSCLC (search), regardless of prior therapies, with a manageable safety profile," said Raul Rodriguez, Rigel's president and CEO.
Expanding GAVRETO's Potential Beyond Lung Cancer
Another significant finding comes from the Phase 2 portion of the ARROW trial in patients with RET (search) fusion-positive solid tumors other than NSCLC (search) and thyroid cancer. The data revealed an ORR of 46.4% (13/28) across various tumor types, with particularly impressive results in pancreatic cancer (search), where all five patients (100%) responded to treatment.
Overall, 10.7% (3/28) of patients achieved complete response (including two with pancreatic cancer (search) and one with cancer of unknown primary) and 35.7% (10/28) achieved partial response. Median PFS was 7 months, median DOR was 11.1 months, and median OS was 10.3 months.
These results validate RET (search) fusions as a tissue-agnostic target with sensitivity to RET inhibition, suggesting GAVRETO's potential to address unmet medical needs across multiple cancer types.
REZLIDHIA Shows Promise in Earlier Treatment Lines for AML
For REZLIDHIA, a post-hoc analysis of the pivotal cohort from the Phase 1/2 study evaluated outcomes in patients with relapsed/refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (search) (AML (search)) who received the drug after either 1-2 or ≥3 prior lines of therapy.
The analysis revealed that patients in the 1-2 prior regimens group showed higher ORR and complete response (CR)/complete response with hematologic improvement (CRh) rates, as well as longer median OS than those with ≥3 prior lines of therapy. This provides a rationale for initiating REZLIDHIA earlier in the R/R treatment paradigm.
"The collective data being presented on REZLIDHIA support its duration of response and potential clinical benefit when used in earlier lines of treatment for R/R AML (search) patients and in primary refractory patients who are traditionally difficult to treat," Rodriguez noted.
Efficacy in Primary Refractory AML
Another important finding comes from a post-hoc analysis of REZLIDHIA in primary refractory AML (search) patients, a population with traditionally poor prognosis. Among 46 patients who were primary refractory to first-line treatment or subsequent induction therapy, REZLIDHIA therapy achieved an ORR of 50% (23/46), with 30% (14/46) achieving a CR/CRh and a median duration of CR/CRh of 17.6 months.
The most common treatment-emergent adverse events were nausea (41%), vomiting (30%), and an increase in white blood cells (30%), with no new safety signals observed. These results suggest REZLIDHIA may be an effective therapeutic option for this difficult-to-treat patient population.
REZLIDHIA as Maintenance Therapy
REZLIDHIA was also evaluated as maintenance therapy in a separate cohort (n=18) of the Phase 2 trial in patients who achieved minimal residual disease (MRD)-positive CR or CR with incomplete blood count recovery (CRi) with prior treatment.
The 4-month relapse-free survival (RFS) was 83% with a median RFS of 18.4 months. At 12 months, RFS was 71% and OS was 89%. RFS at 2 years was 48%. Notably, two patients who had received prior venetoclax therapy entered with a CRi, improved to a CRh, and ultimately achieved a CR during the study.
The most common treatment-emergent adverse events were fatigue (33%), headache (33%), and nausea (28%), with no new safety signals. These results support the potential benefit of switching to REZLIDHIA upon response to therapy.
Comparative Effectiveness Analysis
A matching-adjusted indirect comparison (MAIC) analysis compared the relative treatment effects of REZLIDHIA versus ivosidenib in mIDH1 R/R AML (search), leveraging registrational data for both drugs to match patients using key baseline clinical variables.
Naïve and adjusted rates of response for REZLIDHIA versus ivosidenib were comparable (adjusted point estimate favored REZLIDHIA for CR and ivosidenib for CR+CRh), while a longer duration of CR+CRh was observed with REZLIDHIA. Adjusted OS was similar between the two groups, although the hazard ratio (HR) favored REZLIDHIA.
The researchers noted that these results rely on the assumption of no unmeasured confounders, which reflects a limitation of the methodology.
Impact on Treatment Paradigms
These comprehensive data presentations highlight the growing body of evidence supporting both GAVRETO and REZLIDHIA as important therapeutic options in their respective indications. For GAVRETO, the data reinforces its role in RET (search) fusion-positive NSCLC (search) while suggesting potential expanded use in other RET fusion-positive solid tumors. For REZLIDHIA, the findings support its use earlier in the treatment paradigm for R/R AML (search) and as a maintenance strategy.
The detailed results from these studies will be presented at the upcoming ASCO and EHA conferences, providing the oncology community with valuable insights that could potentially influence treatment decisions and guidelines for patients with these challenging malignancies.