Gavreto
(Pralsetinib)Dosage & Administration
Select patients for treatment with GAVRETO based on the presence of a
Information on FDA-approved tests for
The efficacy of GAVRETO was evaluated in patients with
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.
Efficacy was evaluated in 130 patients with
The median age was 59 years (range: 26 to 85); 51% were female, 40% were White, 50% were Asian, 4.6% were Hispanic/Latino. ECOG performance status was 0-1 (95%) or 2 (3.8%), 99% of patients had metastatic disease, and 41% had either a history of or current CNS metastasis. Patients received a median of 2 prior systemic therapies (range 1–6); 42% had prior anti-PD-1/PD-L1 therapy and 27% had prior kinase inhibitors. A total of 48% of the patients received prior radiation therapy.
Efficacy results for
| Efficacy Parameter | GAVRETO N=130 |
|---|---|
| NE = not estimable | |
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 63 (54, 71) |
| Complete Response, % | 6 |
| Partial Response, % | 57 |
Duration of Response (DOR) | N=82 |
| Median, months (95% CI) | 38.8 (14.8, NE) |
| Patients with DOR ≥ 12-monthsBased on observed duration of response, % | 66 |
For the 54 patients who received an anti-PD-1 or anti-PD-L1 therapy, either sequentially or concurrently with platinum-based chemotherapy, an exploratory subgroup analysis of ORR was 59% (95% CI: 45, 72) and the median DOR was 22.3 months (95% CI: 8.0, NE).
Among the 130 patients with
Efficacy was evaluated in 107 patients with treatment-naïve
The median age was 62 years (range 30 to 87); 53% were female, 49% were White, 45% were Asian, and 2.8% were Hispanic or Latino. ECOG performance status was 0-1 for 99% of the patients and 98% of patients had metastatic disease; 28% had either history of or current CNS metastasis.
Efficacy results for treatment-naïve
| Efficacy Parameter | GAVRETO N=107 |
|---|---|
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 78 (68, 85) |
| Complete Response, % | 7 |
| Partial Response, % | 71 |
Duration of Response (DOR) | N=83 |
| Median, months (95% CI) | 13.4 (9.4, 23.1) |
| Patients with DOR ≥ 12-monthsBased on observed duration of response, % | 45 |
The efficacy of GAVRETO was evaluated in
The median age was 61 years (range: 46 to 74); 67% were male, 78% were White, 22% were Asian, 11% were Hispanic/Latino. All patients (100%) had papillary thyroid cancer. ECOG performance status was 0-1 (100%), all patients (100%) had metastatic disease, and 56% had a history of CNS metastases. 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%).
Efficacy results are summarized in Table 12.
| Efficacy Parameters | GAVRETO N=9 |
|---|---|
| NR = Not Reached; NE = Not Estimable | |
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 89 (52, 100) |
| Complete Response, % | 0 |
| Partial Response, % | 89 |
Duration of Response (DOR) | N=8 |
| Median in months (95% CI) | NR (NE, NE) |
| Patients with DOR ≥ 6 monthsBased on observed duration of response, % | 100 |
The recommended dosage in adults and pediatric patients 12 years and older is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO). (
The recommended dosage of GAVRETO is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO
If a dose of GAVRETO is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for GAVRETO the next day.
Do not take an additional dose if vomiting occurs after GAVRETO but continue with the next dose as scheduled.
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Gavreto Prescribing Information
| Indications and Usage, Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer – Accelerated Approval text removed (1.1) | (8/2023) | |||||||||||||||
| Indications and Usage, RET -Mutant Medullary Thyroid Cancer –Indication Removed (1.2) | (7/2023) | |||||||||||||||
Dosage and Administration (Select patients for treatment with GAVRETO based on the presence of a RET gene fusion (NSCLC or thyroid cancer)[see Clinical Studies (14)] .Information on FDA-approved tests for RET gene fusion (NSCLC) is available at http://www.fda.gov/CompanionDiagnostics.An FDA-approved test for the detection of RET gene fusion (thyroid cancer) is not currently available. | (7/2023) | |||||||||||||||
Dosage and Administration, Dose Modification for Use with CYP3A and/or P-glycoprotein (P-gp) Inhibitors (Avoid coadministration of GAVRETO with any of the following:
If coadministration with any of the above inhibitors cannot be avoided, reduce the current dose of GAVRETO as recommended in Table 3. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume GAVRETO at the dose taken prior to initiating the inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)] .
| (6/2023) | |||||||||||||||
Dosage and Administration, Dose Modification for Use with CYP3A Inducers (Avoid coadministration of GAVRETO with any of the following:
If coadministration with any of the above inducers cannot be avoided, increase the starting dose of GAVRETO as recommended in Table 4starting on Day 7 of coadministration of GAVRETO with the inducer. After the inducer has been discontinued for at least 14 days, resume GAVRETO at the dose taken prior to initiating the inducer [see Drug Interactions (7.1), Clinical Pharmacology (12.3)] .
| (6/2023) | |||||||||||||||
GAVRETO is a kinase inhibitor indicated for treatment of:
- Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer as detected by an FDA approved test (NSCLC). ()
1.1 MetastaticRETFusion-Positive Non-Small Cell Lung CancerGAVRETO is indicated for the treatment of adult patients with metastatic
RETfusion-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 RETfusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). ()1.2RETFusion-Positive Thyroid CancerGAVRETO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic
RETfusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).This indication is approved under accelerated approval based on overall response rate and duration of response
[see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Select patients for treatment with GAVRETO based on the presence of a
Information on FDA-approved tests for
The efficacy of GAVRETO was evaluated in patients with
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.
Efficacy was evaluated in 130 patients with
The median age was 59 years (range: 26 to 85); 51% were female, 40% were White, 50% were Asian, 4.6% were Hispanic/Latino. ECOG performance status was 0-1 (95%) or 2 (3.8%), 99% of patients had metastatic disease, and 41% had either a history of or current CNS metastasis. Patients received a median of 2 prior systemic therapies (range 1–6); 42% had prior anti-PD-1/PD-L1 therapy and 27% had prior kinase inhibitors. A total of 48% of the patients received prior radiation therapy.
Efficacy results for
| Efficacy Parameter | GAVRETO N=130 |
|---|---|
| NE = not estimable | |
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 63 (54, 71) |
| Complete Response, % | 6 |
| Partial Response, % | 57 |
Duration of Response (DOR) | N=82 |
| Median, months (95% CI) | 38.8 (14.8, NE) |
| Patients with DOR ≥ 12-monthsBased on observed duration of response, % | 66 |
For the 54 patients who received an anti-PD-1 or anti-PD-L1 therapy, either sequentially or concurrently with platinum-based chemotherapy, an exploratory subgroup analysis of ORR was 59% (95% CI: 45, 72) and the median DOR was 22.3 months (95% CI: 8.0, NE).
Among the 130 patients with
Efficacy was evaluated in 107 patients with treatment-naïve
The median age was 62 years (range 30 to 87); 53% were female, 49% were White, 45% were Asian, and 2.8% were Hispanic or Latino. ECOG performance status was 0-1 for 99% of the patients and 98% of patients had metastatic disease; 28% had either history of or current CNS metastasis.
Efficacy results for treatment-naïve
| Efficacy Parameter | GAVRETO N=107 |
|---|---|
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 78 (68, 85) |
| Complete Response, % | 7 |
| Partial Response, % | 71 |
Duration of Response (DOR) | N=83 |
| Median, months (95% CI) | 13.4 (9.4, 23.1) |
| Patients with DOR ≥ 12-monthsBased on observed duration of response, % | 45 |
The efficacy of GAVRETO was evaluated in
The median age was 61 years (range: 46 to 74); 67% were male, 78% were White, 22% were Asian, 11% were Hispanic/Latino. All patients (100%) had papillary thyroid cancer. ECOG performance status was 0-1 (100%), all patients (100%) had metastatic disease, and 56% had a history of CNS metastases. 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%).
Efficacy results are summarized in Table 12.
| Efficacy Parameters | GAVRETO N=9 |
|---|---|
| NR = Not Reached; NE = Not Estimable | |
Overall Response Rate (ORR) Confirmed overall response rate assessed by BICR(95% CI) | 89 (52, 100) |
| Complete Response, % | 0 |
| Partial Response, % | 89 |
Duration of Response (DOR) | N=8 |
| Median in months (95% CI) | NR (NE, NE) |
| Patients with DOR ≥ 6 monthsBased on observed duration of response, % | 100 |
The recommended dosage in adults and pediatric patients 12 years and older is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO). (
The recommended dosage of GAVRETO is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO
If a dose of GAVRETO is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for GAVRETO the next day.
Do not take an additional dose if vomiting occurs after GAVRETO but continue with the next dose as scheduled.
Capsules: 100 mg, light blue, opaque, hard hydroxypropyl methylcellulose (HPMC) capsule printed with "BLU-667" on the capsule shell body and "100 mg" on the capsule shell cap.
- Lactation: Advise not to breastfeed. ()
8.2 LactationRisk SummaryThere are no data on the presence of pralsetinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose.
- Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur. ()
8.4 Pediatric UseThe safety and effectiveness of GAVRETO have been established in pediatric patients aged 12 years and older for
RETfusion-positive thyroid cancer. Use of GAVRETO in this age group is supported by evidence from an adequate and well-controlled study of GAVRETO in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of pralsetinib, that the exposure of pralsetinib is expected to be similar between adults and pediatric patients age 12 years and older, and that the course ofRETfusion-positive thyroid cancer is sufficiently similar in adults and pediatric patients to allow extrapolation of data in adults to pediatric patients[see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)].The safety and effectiveness of GAVRETO have not been established in pediatric patients with
RETfusion-positive NSCLC or in pediatric patients younger than 12 years old withRETfusion-positive thyroid cancer.Animal Toxicity DataIn a 4-week repeat-dose toxicology study in non-human primates, physeal dysplasia in the femur occurred at doses resulting in exposures similar to the human exposure (AUC) at the clinical dose of 400 mg. In rats there were findings of increased physeal thickness in the femur and sternum as well as tooth (incisor) abnormalities (fractures, dentin matrix alteration, ameloblast/odontoblast degeneration, necrosis) in both 4- and 13-week studies at doses resulting in exposures similar to the human exposure (AUC) at the clinical dose of 400 mg. Recovery was not assessed in the 13-week toxicology study, but increased physeal thickness in the femur and incisor degeneration did not show evidence of complete recovery in the 28-day rat study.
Monitor growth plates in adolescent patients with open growth plates. Consider interrupting or discontinuing therapy based on the severity of any growth plate abnormalities and based on an individual risk-benefit assessment.
None.