Lorlatinib

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3]

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3]

The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows:

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows:

EXP1 (n = 30, treatment naïve).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP1 (n = 30, treatment naïve).

Objective response rate, 90.0% (95% CI, 73.5%‒97.9%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP1 (n = 30, treatment naïve).

Intracranial response rate (n = 3), 66.7% (95% CI, 9.4%‒99.2%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows:

EXP2 (n = 27, previous crizotinib only) and EXP3A (n = 32, previous crizotinib and chemotherapy).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP2 (n = 27, previous crizotinib only) and EXP3A (n = 32, previous crizotinib and chemotherapy).

Objective response rate, 69.5% (95% CI, 56.1%‒80.8%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP2 (n = 27, previous crizotinib only) and EXP3A (n = 32, previous crizotinib and chemotherapy).

Intracranial response rate (n = 23), 87.0% (95% CI, 66.4%‒97.2%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows:

EXP3B (n = 28, one previous second-generation ALK inhibitor with or without chemotherapy).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP3B (n = 28, one previous second-generation ALK inhibitor with or without chemotherapy).

Objective response rate, 32.1% (95% CI, 15.9%‒52.4%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP3B (n = 28, one previous second-generation ALK inhibitor with or without chemotherapy).

Intracranial response rate (n = 9), 55.6% (95% CI, 21.2%‒86.3%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows:

EXP4 (n = 65, two previous ALK inhibitors with or without chemotherapy) and EXP5 (n = 46, three previous lines of ALK inhibitors, with or without chemotherapy).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP4 (n = 65, two previous ALK inhibitors with or without chemotherapy) and EXP5 (n = 46, three previous lines of ALK inhibitors, with or without chemotherapy).

Objective response rate, 38.7% (95% CI, 29.6%‒48.5%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3] › The number of patients treated, the objective response, and the intracranial response rates in each cohort or pooled cohorts are as follows: › EXP4 (n = 65, two previous ALK inhibitors with or without chemotherapy) and EXP5 (n = 46, three previous lines of ALK inhibitors, with or without chemotherapy).

Intracranial response rate (n = 49), 53.1% (95% CI, 38.3%‒67.5%).

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3]

The median DOR has not been reached for any of the pooled cohorts.

In an open-label ongoing phase II study with multiple cohorts, patients with metastatic ALK-rearranged NSCLC were enrolled into six ALK expansion (EXP) cohorts on the basis of their ALK status and treatment history.[39] They received lorlatinib 100 mg once daily continuously in 21-day cycles. The primary end point was overall and intracranial tumor response by independent central review, as assessed in key pooled subgroups.[39][Level of evidence C3]

The most common adverse event was hypercholesterolemia (16% grade 3–4), and 3% of patients discontinued treatment due to adverse events.