Amivantamab Plus Chemotherapy Reduced Risk of Disease Progression, Death in Patients With NSCLC


Compared to chemotherapy alone, amivantamab plus chemotherapy treatment with and without lazertinib had also demonstrated positive trends in OS and ORR in patients with NSCLC.

Results from the phase 3 study MARIPOSA-2 (NCT04988295) indicates that, compared to chemotherapy alone, amivantamab-vmjw (Rybrevant; Janssen Pharmaceutical) with or without lazertinib (Leclaza; Johnson & Johnson) and combined with osimertinib (Tagrisso; AstraZeneca) reduced the risk of disease progression or death by 56% and 52%, respectively, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with either epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution, after disease progression on or after osimertinib. Trial results also showed both amivantamab regimens had significantly improved objective response rate (ORR), intracranial progression-free survival (PFS), and duration of response (DOR). The data were presented at the 2023 European Society of Medical Oncology (ESMO) Congress.

Elderly patient undergoing IV chemotherapy

Image credit: Monkey Business |

MARIPOSA-2 is a randomized, open-label phase 3 study that evaluated the efficacy and safety of 2 combination regimens of amivantamab either with or without lazertinib in addition to chemotherapy. A total of 657 enrolled patients were randomly assigned to receive treatment with amivantamab plus chemotherapy with lazertinib, amivantamab plus chemotherapy, or chemotherapy alone. The study’s primary endpoint was PFS and secondary endpoints included overall survival (OS), DOR, time to subsequent therapy, second PFS, and intracranial PFS.

The study results indicate that, compared to chemotherapy alone, amivantamab plus chemotherapy had reduced the risk of disease progression or death by 52% (HR = 0.48; 95% CI, 0.36-0.64; P < 0.001), and amivantamab plus chemotherapy with lazertinib had reduced the risk by 56% (HR = 0.44; 95% CI, 0.35-0.56; P < 0.001). The improved PFS was consistent across all pre-specified patient subgroups, including race, age, sex, history of brain metastasis, smoking history, and lines of prior osimertinib therapy.

"[Amivantamab] plus chemotherapy, given with and without lazertinib, showed consistent disease control across all pre-specified patient subgroups in the MARIPOSA-2 study," said Craig Tendler, MD, vice president, late development and global medical affairs, Janssen Research & Development, LLC, in a press release.

In addition, patients treated with amivantamab plus chemotherapy had presented an ORR of 64% and amivantamab plus chemotherapy with lazertinib demonstrated an ORR of 63%, compared to an ORR of 36% in the patients treated with only chemotherapy. Further, amivantamab plus chemotherapy and amivantamab plus chemotherapy and lazertinib had reduced the risk of intracranial progression or death by 45% and 42% respectively, compared to chemotherapy alone (HR = 0.55; 95% CI, 0.38-0.79; P = 0.001 and HR = 0.58; 95% CI, 0.44-0.78; P < 0.001, respectively).

Further, early OS data indicates a positive trend for amivantamab plus chemotherapy compared with chemotherapy alone (HR = 0.77; 95% CI, 0.49-1.21); however, there was no difference presented between amivantamab plus chemotherapy and lazertinib compared with chemotherapy alone (HR = 0.96; 95% CI, 0.67-1.35).

"The promising results from the MARIPOSA-2 study show that by combining [amivantamab] with chemotherapy, both with and without lazertinib, patients achieved longer PFS compared with chemotherapy alone," said presenting author Antonio Passaro, MD, PhD, medical oncologist of the division of thoracic oncology, European Institute of Oncology in Milan, Italy, in the press release. "The efficacy seen across the 2 [amivantamab] regimens suggests that this treatment combination may address the diverse and often varied resistance that can occur in the post-osimertinib setting."

The most common adverse effects (AEs) in the amivantamab regimen groups were hematologic, EGFR, and MET-related complications, with amivantamab plus chemotherapy presenting lower rates of hematologic AEs than amivantamab plus chemotherapy with lazertinib. Serious AEs occurred in 52% of patients who received amivantamab plus chemotherapy with lazertinib, 32% in patients who received amivantamab plus chemotherapy with lazertinib, and 20% of patients who received chemotherapy alone. Further, rates of venous thromboembolism were higher in the amivantamab groups; however, they were only grade 1 or 2 in severity. The safety profile for amivantamab was consistent with prior research.

"These encouraging results reinforce the distinct profile of [amivantamab]-based regimens as potential practice-changing treatment options and mark another important key milestone in our pursuit to transform the treatment of EGFR-mutated NSCLC," said Tendler in the press release.


Johnson & Johnson. Phase 3 MARIPOSA-2 Study Shows RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy Given with or without Lazertinib Reduced Risk of Disease Progression or Death by 56 and 52 Percent Respectively in Patients with EGFR-Mutated Non-Small Cell Lung Cancer who Progressed on or after Osimertinib. News release. October 23, 2023. Accessed October 25, 2023.

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