ARROW
A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors
Phase 1/2NCT03037385
- Population
- Advanced or metastatic RET-mutant medullary thyroid cancer (treatment-naive, or previously treated with cabozantinib or vandetanib) and RET fusion-positive thyroid cancer
- Design
- Multi-cohort, open-label phase 1/2 study in 13 countries at 71 sites. Phase 2 patients received pralsetinib 400 mg once daily; phase 2 primary endpoints were overall response rate (RECIST 1.1, masked independent central review) and safety. This record covers the thyroid cancer cohorts.
- Primary endpoint
- ORR
- Arms
- Pralsetinib (experimental): Pralsetinib 400 mg orally once daily
- People
- Subbiah V, senior author Taylor MH
Show the numbers
| Endpoint | Analysis | Pralsetinib | Control | Effect |
|---|---|---|---|---|
| ORRTreatment-naive RET-mutant medullary thyroid cancer with baseline measurable disease (enrolled by 11 July 2019) | interimSubbiah 2021 | 71% (48–89%) | — | 15 of 21 patients responded; all responses confirmed. Patients had to have received pralsetinib by the enrolment cut-off of 11 July 2019 for the efficacy analysis; the data cut-off was 22 May 2020 (full text, Methods). |
| ORRRET-mutant medullary thyroid cancer previously treated with cabozantinib or vandetanib, or both, with baseline measurable disease | interimSubbiah 2021 | 60% (46–73%) | — | 33 of 55 patients responded; all responses confirmed. Enrolment cut-off for the efficacy analysis 11 July 2019; data cut-off 22 May 2020 (full text, Methods). |
| ORRPreviously treated RET fusion-positive thyroid cancer with baseline measurable disease | interimSubbiah 2021 | 89% (52–100%) | — | 8 of 9 patients responded; all responses confirmed. Enrolment cut-off for the efficacy analysis 11 July 2019; data cut-off 22 May 2020 (full text, Methods). Enrolment of RET fusion-positive thyroid cancer was ongoing at the interim analysis. Grade 3 or worse treatment-related adverse events in 142 patients enrolled by 22 May 2020 included hypertension (17%), neutropenia (13%), lymphopenia (12%) and anaemia (10%); one patient (1%) died of a treatment-related adverse event. |
| ORRRET-mutant medullary thyroid cancer with prior cabozantinib and/or vandetanib, measurable disease (61 patients) | long term-updateSubbiah 2024 | 55.7% (42.4–68.5%) | — | 61 patients. |
| ORRTreatment-naive RET-mutant medullary thyroid cancer, measurable disease (62 patients) | long term-updateSubbiah 2024 | 77.4% (65.0–87.1%) | — | 62 patients. |
| ORRPreviously treated RET fusion-positive thyroid cancer, measurable disease (22 patients) | long term-updateSubbiah 2024 | 90.9% (70.8–98.9%) | — | 22 patients; prior systemic therapy included radioactive iodine. |
| PFSRET-mutant medullary thyroid cancer with prior cabozantinib and/or vandetanib (61 patients) | long term-updateSubbiah 2024 | median 25.8 months | — | Median duration of response was also 25.8 months. In treatment-naive RET-mutant medullary thyroid cancer, median duration of response and median PFS were not reached. |
| PFSPreviously treated RET fusion-positive thyroid cancer (22 patients) | long term-updateSubbiah 2024 | median 25.4 months | — | Median duration of response was 23.6 months. |
| Endpoint | Analysis | Pralsetinib | Control | Effect |
|---|---|---|---|---|
| ORRTreatment-naive RET-mutant medullary thyroid cancer with baseline measurable disease (enrolled by 11 July 2019) | interimSubbiah 2021 | 71% (48–89%) | — | 15 of 21 patients responded; all responses confirmed. Patients had to have received pralsetinib by the enrolment cut-off of 11 July 2019 for the efficacy analysis; the data cut-off was 22 May 2020 (full text, Methods). |
| ORRRET-mutant medullary thyroid cancer previously treated with cabozantinib or vandetanib, or both, with baseline measurable disease | interimSubbiah 2021 | 60% (46–73%) | — | 33 of 55 patients responded; all responses confirmed. Enrolment cut-off for the efficacy analysis 11 July 2019; data cut-off 22 May 2020 (full text, Methods). |
| ORRPreviously treated RET fusion-positive thyroid cancer with baseline measurable disease | interimSubbiah 2021 | 89% (52–100%) | — | 8 of 9 patients responded; all responses confirmed. Enrolment cut-off for the efficacy analysis 11 July 2019; data cut-off 22 May 2020 (full text, Methods). Enrolment of RET fusion-positive thyroid cancer was ongoing at the interim analysis. Grade 3 or worse treatment-related adverse events in 142 patients enrolled by 22 May 2020 included hypertension (17%), neutropenia (13%), lymphopenia (12%) and anaemia (10%); one patient (1%) died of a treatment-related adverse event. |
| ORRRET-mutant medullary thyroid cancer with prior cabozantinib and/or vandetanib, measurable disease (61 patients) | long term-updateSubbiah 2024 | 55.7% (42.4–68.5%) | — | 61 patients. |
| ORRTreatment-naive RET-mutant medullary thyroid cancer, measurable disease (62 patients) | long term-updateSubbiah 2024 | 77.4% (65.0–87.1%) | — | 62 patients. |
| ORRPreviously treated RET fusion-positive thyroid cancer, measurable disease (22 patients) | long term-updateSubbiah 2024 | 90.9% (70.8–98.9%) | — | 22 patients; prior systemic therapy included radioactive iodine. |
| PFSRET-mutant medullary thyroid cancer with prior cabozantinib and/or vandetanib (61 patients) | long term-updateSubbiah 2024 | median 25.8 months | — | Median duration of response was also 25.8 months. In treatment-naive RET-mutant medullary thyroid cancer, median duration of response and median PFS were not reached. |
| PFSPreviously treated RET fusion-positive thyroid cancer (22 patients) | long term-updateSubbiah 2024 | median 25.4 months | — | Median duration of response was 23.6 months. |
- Pralsetinib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pralsetinib |
|---|---|
| 0 | 100.0% |
| 16 | 65.1% |
| 32 | 42.3% |
| 48 | 27.5% |
| 65 | 17.4% |
- Pralsetinib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pralsetinib |
|---|---|
| 0 | 100.0% |
| 16 | 64.6% |
| 32 | 41.8% |
| 48 | 27.0% |
| 64 | 17.4% |
Appears in
Sources
Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, et al. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021;9(8):491-501.
Subbiah V, Hu MI, Mansfield AS, Taylor MH, Schuler M, Zhu VW, et al. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study. Thyroid. 2024;34(1):26-40.