Amivantamab plus chemotherapy

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

The median follow-up was 8.7 months.

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

The median PFS was 6.3 months (95% CI, 5.6–8.4) in the amivantamab-plus-chemotherapy arm, 8.3 months (95% CI, 6.8–9.1) in the amivantamab-plus-lazertinib-plus-chemotherapy arm and 4.2 months (95% CI, 4.0–4.4) in the chemotherapy-alone arm (HR, 0.48; 95% CI, 0.36–0.64; P < .0001).[30][Level of evidence B1]

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

The confirmed objective response rate was 64% (95% CI, 55%–72%) in the amivantamab-plus-chemotherapy arm, 63% (95% CI, 57%–69%) in the amivantamab-plus-lazertinib-plus-chemotherapy arm, and 36% (95% CI, 30%–42%) in the chemotherapy-alone arm (P < .0001).

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

At the time of this first interim OS analysis, the HRdeath was 0.77 (95% CI, 0.49–1.21) for amivantamab plus chemotherapy versus chemotherapy alone, and 0.96 (95% CI, 0.67–1.35) for amivantamab plus lazertinib and chemotherapy versus chemotherapy alone.

The global phase III MARIPOSA-2 trial (NCT04988295) included 657 patients with locally advanced or metastatic NSCLC and EGFR variants (EGFR exon 19 deletions or EGFR L858R variants). Patients had disease progression after receiving prior osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive amivantamab plus lazertinib plus chemotherapy, chemotherapy alone, or amivantamab and chemotherapy. Patients with brain metastases were eligible if their intracranial disease was clinically stable and they were asymptomatic and receiving stable doses of steroids. The dual primary end points were (1) PFS in patients who received amivantamab plus chemotherapy versus chemotherapy alone and (2) in patients who received amivantamab plus lazertinib and chemotherapy versus chemotherapy alone. Key secondary end points included objective response rate per blinded independent central review and OS.[30]

Patients in the amivantamab-plus-chemotherapy arm had lower rates of hematologic adverse events than those in the amivantamab-plus-lazertinib-plus-chemotherapy arm. Hematologic toxicities were observed in the patients in the amivantamab-plus-lazertinib-plus-chemotherapy arm that necessitated a regimen change to start lazertinib therapy after carboplatin completion.