For Patients

Clinical Trial Information for GAVRETO

Study design in the RET+ NSCLC population1

Efficacy and safety with GAVRETO (400 mg orally once daily) were evaluated in patients with RET fusion+ mNSCLC in the ARROW study, a phase 1/2, nonrandomized, open-label, single-arm, multicohort, multicenter clinical trial. Patients with asymptomatic central nervous system metastases, including patients with stable or decreasing steroid use within 2 weeks prior to study entry, were enrolled.

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.

mNSCLC=metastatic non–small cell lung cancer; RECIST=Response Evaluation Criteria in Solid Tumors; RET+=rearranged during transfection positive.

GAVRETO was studied in first-line and previously treated RET+ mNSCLC patient populations similar to those seen in real-world practice1,33

  Treatment-naïve patients (n=27) Previously platinum-treated patients (n=87)
Median age (range), years 65 years (30-87) 60 years (28-85)
Gender 52% female, 48% male 49% female, 51% male
Race/ethnicity 59% White, 33% Asian, 4% Hispanic/Latino 53% White, 35% Asian, 6% Hispanic/Latino
ECOG status 0-1: 96%
2: 4%		 0-1: 94%
2: 6%
RET fusion partner 70% KIF5B, 11% CCDC6 75% KIF5B, 17% CCDC6
History of or current
brain metastases
at baseline		 37% 43%
Prior therapy - 45% PD-1/PD-L1 inhibitor
25% prior kinase inhibitors
Patient identification 67% NGS
  • 41% tumor samples
  • 22% blood or plasma
  • 4% unknown
33% FISH		 77% NGS
  • 45% tumor samples
  • 26% blood or plasma
  • 6% unknown
21% FISH
2% other

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

NCCN Guideline Recommendations
See guideline recommendations for pralsetinib (GAVRETO)
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Safety for GAVRETO
See RET+ mNSCLC safety for GAVRETO

Explore the safety results for all RET+ mNSCLC patients studied.

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Important Safety Information & Indications

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.

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      GAVRETO Prescribing Information. Genentech, Inc. September 2022.

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