GAVRETO demonstrated robust and durable response in RET+ advanced thyroid cancers1

RET=rearranged during transfection. 

In preclinical studies, pralsetinib was designed for potent and selective inhibition of RET

ARROW study design in the thyroid cancer population

Efficacy and safety with GAVRETO (400 mg orally once daily) was evaluated in patients with advanced or metastatic RET-mutant+ MTC and RET fusion+ thyroid cancer in the ARROW study, a phase 1/2, nonrandomized, open-label, single-arm, multicohort, multicenter clinical trial. All patients must have had a non-resectable RET-altered solid tumor or MTC per local assessment of tumor tissue and/or blood. All patients must also have had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.4

See baseline characteristics

MTC=medullary thyroid cancer.

Efficacy results with GAVRETO

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR), as assessed by a blinded independent central review (BICR) according to RECIST v1.1. 

RECIST=Response Evaluation Criteria in Solid Tumors.

In advanced or metastatic RET-mutant MTC

CABOZANTINIB AND VANDETANIB-NAÏVE

TREATMENT NAÏVE PATIENTS (n=21)
TREATMENT NAÏVE PATIENTS (n=21)

PRIOR CABOZANTINIB AND/OR VANDETANIB

PREVIOUSLY PLATINUM-TREATED PATIENTS (n=55)
PREVIOUSLY PLATINUM-TREATED PATIENTS (n=55)

In advanced or metastatic RET fusion+ thyroid cancer

TREATMENT NAIVE PATIENTS (n=9)
TREATMENT NAIVE PATIENTS (n=9)

CI=confidence interval; CR=complete response; NE=not estimable; NR=not reached; PR=partial response.


Demographic characteristics in the advanced thyroid cancer population at baseline

  MTC: cabozantinib and
vandetanib-naïve patients
(n=29)
MTC: previously cabozantinib
and/or vandetanib treated
patients
(n=55)
RET fusion-positive
thyroid cancer§
(n=9)
Median age 61 years (19-81) 59 years (25-83) 61 years (46-74)
Gender 28% female
72% male
31% female
69% male
33% female
67% male
Race/ethnicity 76% White
17% Asian
3.4% Hispanic/Latino
78% White
5% Asian
5% Hispanic/Latino
78% White
22% Asian
11% Hispanic/Latino
ECOG status 0-1: 100% 0-1: 95%
2: 5%
0-1: 100%
History of CNS metastases at baseline 14% 7% 56%
Patient Identification 90% NGS
  • 52% tumor sample
  • 35% plasma
  • 3.4% blood
10% PCR
73% NGS
  • 55% tumor sample
  • 18% plasma
26% PCR
2% other
89% NGS
11% FISH

ECOG=Eastern Cooperative Oncology Group; FISH=fluorescence in situ hybridization; NGS=next generation sequencing; PCR=polymerase chain reaction; PD-1/PD-L1=programmed cell death protein 1/programmed death ligand 1.

*Calculated using the proportion of responders with an observed duration of response at least 6 months or greater. 
97% of patients had metastatic disease. 28% had received up to 3 lines of prior systemic therapy (including 10% PD-1/PD-L1 inhibitors, 10% radioactive iodine, 3.4% kinase inhibitors). 
Patients had received a median of 2 prior therapies (range 1-7). The primary mutations in RET-mutant MTC previously treated with cabozantinib or vandetanib are described in Table 10 of the Full Prescribing Information for GAVRETO.
§All patients had papillary thyroid cancer. All patients had metastatic disease. Patients had received a median of 2 prior therapies (range 1-8). Prior systemic treatments included prior radioactive iodine (100%) and prior sorafenib and/or lenvatinib (56%).

INDICATIONS

GAVRETO® (pralsetinib) is indicated for the treatment of:

  • Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Interstitial Lung Disease (ILD)/Pneumonitis occurred in 10% of patients who received GAVRETO, including 2.7% with Grade 3/4, and 0.5% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD.

Hypertension occurred in 29% of patients, including Grade 3 hypertension in 14% of patients. Overall, 7% had their dose interrupted and 3.2% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.

Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.1% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 69% of patients, including Grade 3/4 in 5% and increased alanine aminotransferase (ALT) occurred in 46% of patients, including Grade 3/4 in 6%. The median time to first onset for increased AST was 15 days (range: 5 days to 1.5 years) and increased ALT was 22 days (range: 7 days to 1.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.

Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.

Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.

Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the final dose. Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the final dose.

Common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased AST, increased ALT, decreased platelets and increased alkaline phosphatase.

Avoid coadministration of GAVRETO with strong CYP3A inhibitors or combined P-gp and strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please click here to see the full Prescribing Information for GAVRETO.

    • GAVRETO® (pralsetinib). Prescribing Information. Blueprint Medicines Corporation; Cambridge, MA. December 2020.

      GAVRETO® (pralsetinib). Prescribing Information. Blueprint Medicines Corporation; Cambridge, MA. December 2020.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed June 1, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed June 1, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Data on file. Blueprint Medicines Corporation; Cambridge, MA. 2020.

      Data on file. Blueprint Medicines Corporation; Cambridge, MA. 2020.

    • Phase 1/2 study of the highly-selective RET inhibitor, pralsetinib (BLU-667), in patients with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors (ARROW). https://clinicaltrials.gov/ct2/show/NCT03037385. Accessed April 22, 2021. 

      Phase 1/2 study of the highly-selective RET inhibitor, pralsetinib (BLU-667), in patients with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors (ARROW). https://clinicaltrials.gov/ct2/show/NCT03037385. Accessed April 22, 2021.