Entrectinib

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

The objective response rate in 54 patients was 57% (95% CI, 43.2%−70.8%). Seven percent of patients had a complete response and 50% had a partial response. In patients with baseline CNS disease, 50% achieved a response (all partial responses), whereas in patients without baseline CNS disease, 60% achieved a response (10% complete response; 50% partial response).[82][Level of evidence C3]

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

The median DOR in efficacy-evaluable patients was 10.4 months (95% CI, 7.1−NE). In patients with baseline CNS disease DOR was not estimable, and in patients with no baseline CNS disease it was 12.9 months (95% CI, 7.1−NE).

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

Among 10 patients with NSCLC, the response rate was 70% (95% CI, 35%−93%) and DOR ranged between 1.9 months and 20.1 months. For more information, see the prescribing information.

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

The safety-evaluable population consisted of 68 patients with NTRK fusion–positive tumors. Most treatment-related adverse events were grade 1 or 2 and reversible. The most frequent grade 3 or 4 treatment-related adverse events were increased weight gain (10%) and anemia (12%). Serious treatment-related adverse events were reported in 7 (10%) patients. Three (4%) patients had dose interruptions and 27 (40%) patients had dose reductions due to treatment-related adverse events. There were no treatment-related deaths.

The safety and clinical activity of entrectinib in NTRK inhibitor-naïve patients with metastatic or locally-advanced solid tumors (including NSCLC) and NTRK1, NTRK2, or NTRK3 gene fusions was determined by integrated analysis of three early-phase, multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[82] Treatment consisted of entrectinib administered orally at a dose of at least 600 mg once per day. The primary end points were objective response rate and median DOR, which were assessed by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Identification of positive NTRK gene fusion status was conducted prospectively in local laboratories or a central laboratory using various nucleic acid–based tests. Of 54 patients in the NTRK gene fusion–positive efficacy-evaluable population, 20 (37%) had received no previous systemic therapy, 11 (20%) had received one previous systemic therapy, and 23 (43%) had received two or more systemic therapies. Twelve (22%) patients had CNS disease at baseline. Ten (19%) patients had NSCLC. Fifty-two (96%) patients had NTRK gene fusions detected by NGS and 2 (4%) had NTRK gene fusions detected by other nucleic acid–based tests.

Median PFS was 11.2 months (95% CI, 8.0−14.9). In patients with baseline CNS disease, median PFS was 7.7 months (95% CI, 4.7−NE), and it was 12 months (95% CI, 8.7−15.7) in patients with no baseline CNS disease.