Clinical Results for GAVRETO

GAVRETO demonstrated a robust and durable response with or without prior therapy in RET+ mNSCLC1

Efficacy results in treatment-naïve patients from the USPI1,34

Overall Response Rate (n=27)

70% ORR

(95% CI: 50%-86%)

Duration of and Time to Response (n=19)1,34

  • 58% of patients continued to respond to treatment at 6 months
  • Median time to first response was 1.9 months
    (range: 1.4 months-5.6 months)34

Patients enrolled by July 11, 2019. Data cutoff: Feb 13, 2020.
Based on observed duration of response.
CI=confidence interval; CR=complete response; DoR=duration of response; mNSCLC=metastatic non–small cell lung cancer; NE=not estimable; ORR=overall response rate; PR=partial response; RET+=rearranged during transfection positive.

U.S. Prescribing Information (USPI)35

Per protocol, all treatment-naïve patients were not eligible for platinum-based chemotherapy based on an investigator assessment

Exploratory Analyses35

In July 2019, the protocol was amended to expand the eligibility criteria to include patients who were eligible for standard therapy

Exploratory follow-up analyses34

These analyses include treatment-naïve patients enrolled by May 22, 2020, which include the patients from the pivotal analysis in the USPI. Results of these exploratory follow-up analyses are not included in GAVRETO labeling. As these were not prespecified analyses, data must be interpreted with caution.

ALL TREATMENT-NAÏVE PATIENTS34

Overall Response Rate (n=68)

79% ORR

(95% CI: 68%-88%)

Duration of Response (n=54)

POST HOC ANALYSES OF TREATMENT-NAÏVE PATIENTS34

Initially, the ARROW protocol included treatment-naïve patients who were not candidates for standard therapy. In July 2019, the protocol was amended to expand the eligibility criteria to include patients who were eligible for standard therapy.35

Pre-protocol amendment (n=43)

PR=65%, CR=9% (95% CI: 59%-87%)
Median DoR (n=32): 11 months (7.4 months-NR)

Select baseline characteristics

  • Median age: 65 years (30-87)
  • Gender: female 44%, male 56%
  • History of or current CNS metastases at baseline: 35%

Post-protocol amendment (n=25)

All responses were partial (95% CI: 69%-98%)
Median DoR (n=22): Not Reached (NR-NR)

Select baseline characteristics

  • Median age: 54 years (35-80)
  • Gender: female 56%, male 44%
  • History of or current CNS metastases at baseline: 28%

All other baseline characteristics were generally balanced between the pivotal data included in the USPI and exploratory follow-up populations.1,34
Patients enrolled by May 22, 2020. Data cutoff: Nov 6, 2020.
CNS=central nervous system; NR=not reached.

Efficacy results in previously platinum-treated patients from the USPI1,34

Overall Response Rate (n=87)

57% ORR

(95% CI: 46%-68%)

Duration of and Time to Response (n=50)1,34

  • 80% of patients continued to respond to treatment at 6 months
  • Median time to first response was 1.8 months
    (range: 1.3 months-9.1 months)34

Patients enrolled by July 11, 2019. Data cutoff: Feb 13, 2020.
Based on observed duration of response.

Consistent responses were observed with GAVRETO, including CNS activity, across previously treated subgroups1

CNS Activity

Brain metastases at baseline (n=8)§

DoR at 6 months: 75%

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).34
§
No patients received radiation therapy (RT) to the brain within 2 months prior to study entry.

Prior PD-1/PD-L1 Inhibitor

Exploratory Analysis

Disease control rate in treatment-naïve and previously treated mNSCLC patients34

Disease control rate (DCR), a prespecified 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.35

  • Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR or CR nor sufficient increase to qualify for progressive disease (PD), per RECIST v1.135,36
  • 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

Treatment-naïve patients (n=27)

Previously platinum-treated patients (n=87)

Patients enrolled by July 11, 2019. Data cutoff: Feb 13, 2020.

PD-1=programmed cell-death protein 1; PD-L1=programmed death-ligand 1.

NCCN Guideline Recommendations
See guideline recommendations for pralsetinib (GAVRETO)