Efficacy data for GAVRETO

GAVRETO was studied in patient populations representative of those seen in the real world1,2

Efficacy and safety with GAVRETO (400 mg orally once daily) were evaluated in patients with RET fusion-positive 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.1,3

mNSCLC=metastatic non–small cell lung cancer; RET=rearranged during transfection.

Demographic characteristics at baseline1

 Treatment-naïve patients
(n=107)		Previously platinum-treated patients
(n=130)
Median age62 years (30-87)59 years (26-85)
Gender53% female
47% male		51% female
49% male
Race/ethnicity49% White
45% Asian
3% Hispanic/Latino		40% White
50% Asian
5% Hispanic/Latino
ECOG status
0-199%95%
2-4%
History of or current CNS metastases at baseline28%41%
RET fusion partner
KIF5B71%70%
CCDC618%19%
Prior therapy type*
PD-1/PD-L1 inhibitor-42%
Kinase inhibitors-27%
Patient identification68% NGS
(30% tumor sample, 17% blood or plasma, 22% unknown)
19% FISH		80% NGS
(37% tumor sample, 15% blood or plasma, 28% unknown)
13% FISH
2% other

*Previously platinum-treated patients received a median of 2 prior systemic therapies (range 1-6).1
CNS=central nervous system; 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.

Lung patient safety
GAVRETO is an approved therapy for both treatment-naïve and previously treated mNSCLC patients.

GAVRETO demonstrated strong and durable response regardless of prior treatment

Efficacy results in treatment-naïve patients1,4

Overall Response Rate (n=107)1

78% ORR

78% ORR*

(95% CI: 68%-85%)

Duration of and Time to Response* (n=83)1,4

Median DOR 13.4 months
  • 45% of patients continued to respond to treatment at ≥12 months1†
  • Median time to first response was 1.8 months
    (range: 0.9 months-6.1 months)4

Disease control rate in treatment-naïve patients3

Treatment-naïve patients (n=107)‡

TREATMENT NAIVE PATIENTS (n=107)

‡Disease control rate (DCR), a secondary endpoint, was assessed in the subsets of patients in the efficacy populations with sufficient evidence of a RET fusion and baseline measurable disease confirmed on blinded independent central review. DCR is defined as ORR (CR + PR) + SD.5

  • Importantly, SD can reflect the natural history of the disease and may not be due to a direct therapeutic effect. Therefore, please interpret these results with caution

SD=stable disease.

Efficacy results in previously platinum-treated patients1,4

Overall Response Rate (n=130)1

63% ORR

63% ORR*

(95% CI: 54%-71%)

Duration of and Time to Response* (n=82)1,4

Median DOR 38.8 months
  • 66% of patients continued to respond to treatment at ≥12 months1†
  • Median time to first response was 1.8 months
    (range: 1.3 months-11.4 months)4

Patients enrolled by July 11, 2019. Data cutoff: March 4, 2022.
*ORR and DoR were assessed by BICR, according to RECIST v1.1.
†Based on observed DoR.
BICR=blinded independent central review; CI=confidence interval; CR=complete response; DoR=duration of response; NE=not estimable; ORR=overall response rate; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors.

Disease control rate in platinum-treated patients with mNSCLC4

Previously platinum-treated patients (n=130)‡

PREVIOUSLY PLATINUM-TREATED PATIENTS (n=130)

‡Disease control rate (DCR), a secondary endpoint, was assessed in the subsets of patients in the efficacy populations with sufficient evidence of a RET fusion and baseline measurable disease confirmed on blinded independent central review. DCR is defined as ORR (CR + PR) + SD.5

  • Importantly, SD can reflect the natural history of the disease and may not be due to a direct therapeutic effect. Therefore, please interpret these results with caution

Patients with brain metastases and prior PD-L1 treatment benefited from GAVRETO1

CNS ACTIVITY1

Brain metastases at baseline (n=10)§

70%

of previously platinum-treated patients with measurable disease had a response

71%

DoR
 ≥6 months

20% of patients had a complete response

§No patients received radiation therapy (RT) to the brain within 2 months prior to study entry.

CNS Activity brain chart

Courtesy of Dr. Kim. Image is from a patient in the ARROW trial who achieved complete CNS response. Image is for illustrative purposes only; individual results may vary. According to the protocol, images were to be performed every 8 weeks (±7 days).4

PRIOR PD-1/PD-L1 INHIBITOR

EXPLORATORY ANALYSIS1

(n=54)

59% ORR

(95% CI: 45%-72%)

Median DoR

22.3% months

(95% CI: 8.0 months-NE)

Lung patient safety
GAVRETO demonstrated strong and durable response regardless of prior treatment
NEXT: Safety
Safety for GAVRETO
See RET+ mNSCLC safety for GAVRETO

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

See now

GAV_LNG-25015 0525

References:

 

1. GAVRETO® [Package insert], South San Francisco, CA: Rigel Pharmaceuticals, Inc.

 

2. Hess LM, Han Y, Zhu YE, Bhandari NR, Sireci A. Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States. BMC Cancer. 2021;21(28):1-12.

 

3. Phase 1/2 study of the highly-selective RET inhibitor, pralsetinib (BLU-667), in participants with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors (ARROW). https://clinicaltrials.gov/ct2/show/NCT03037385. Accessed May 7, 2025.

 

4. GAVRETO: Data on file, Rigel Pharmaceuticals, Inc. June 2024.

 

5. Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021;22(7):959-969.

Indications & Important Safety Information

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 fusion-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).

IMPORTANT SAFETY INFORMATION

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal ILD/pneumonitis can occur in patients treated with GAVRETO. Pneumonitis occurred in 12% of patients who received GAVRETO, including 3.3% with Grade 3-4, and 0.2% 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 35% of patients, including Grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% 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 1.5% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 49% of patients, including Grade 3 or 4 in 7% and increased alanine aminotransferase (ALT) occurred in 37% of patients, including Grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range: 5 days to 2.5 years) and increased ALT was 24 days (range: 7 days to 3.7 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.

Hemorrhagic Events: Serious, including fatal, hemorrhagic events can occur with GAVRETO. Grade ≥3 events occurred in 4.1% 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.

Risk of Impaired Wound Healing: 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.

Embryo-Fetal Toxicity: 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 last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the last dose.

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

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

Lactation: 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.

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

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