SUMMARY

• RYBREVANT (amivantamab-vmjw) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).¹
• LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor (TKI).²
• No pharmacokinetics (PK) data regarding RYBREVANT blood-brain barrier (BBB) or central nervous system (CNS) penetration were identified in the published literature.
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT and lazertinib combination therapy (open-label, n=429) vs osimertinib (double-blind, n=429) vs lazertinib (double-blind, n=216) as first-line treatment in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R) locally advanced or metastatic NSCLC.^2-4 
  • For patients with a history of brain metastases, the blinded independent central review (BICR)-assessed median progression-free survival (PFS) was 18.3 months (95% confidence interval [CI], 16.6-23.7) for RYBREVANT plus lazertinib and 13 months (95% CI, 12.2-16.4) for osimertinib (hazard ratio [HR], 0.69; 95% CI, 0.53-0.92). For patients without a history of brain metastases, median PFS was 27.5 months (95% CI, 22.1-not estimable [NE]) for RYBREVANT plus lazertinib and 19.9 months (95% CI, 16.6-22.9) for osimertinib (HR, 0.69; 95% CI, 0.53‑0.89).⁴ 
  • For patients with and without a history of brain metastases, the HR for overall survival (OS) was 0.67 (95% CI, 0.5-0.9) and 0.82 (95% CI, 0.62-1.08), respectively, for RYBREVANT plus lazertinib vs osimertinib.⁵
• CHRYSALIS-2 (NCT04077463) is an ongoing, phase 1/1b, open-label, multicenter, dose-escalation (phase 1) and dose-expansion (phase 1b) study evaluating the efficacy, safety, PK, and immunogenicity of lazertinib as monotherapy and in combination with RYBREVANT in adult patients with metastatic or unresectable NSCLC harboring EGFR mutations (Exon19del or Exon 21 L858R, Exon 20 insertion [Exon20ins], or uncommon EGFR mutations) with disease progression on previous standard of care (SOC) treatment.⁶ 
  • Besse et al (2025)⁷ reported results from cohort A of the CHRYSALIS-2 study, which included patients with EGFR Exon19del or Exon 21 L858R mutations who received RYBREVANT plus lazertinib (n=162) after prior treatment with osimertinib and platinum-based chemotherapy.
    • For patients with vs without brain metastases at baseline, the BICR-assessed overall response rate (ORR) was 36% (95% CI, 26-47) vs 32% (95% CI, 22-44), and clinical benefit rate (CBR) was 56% (95% CI, 45-66) vs 61% (95% CI, 49-72), with 0% vs 1% of patients achieving complete response (CR) and 36% vs 31% achieving partial response (PR).⁸
  • Lee et al (2023)⁹ reported results from the LACP cohort of the CHRYSALIS-2 study, which included patients with EGFR-mutated advanced NSCLC post-TKI who received RYBREVANT-lazertinib-chemotherapy (pemetrexed and carboplatin; n=20).
    • For patients with a history of brain metastases, the investigator-assessed median PFS, ORR, and CBR were 6.7 months (95% CI, 1.4-NE), 50% (95% CI, 19-81), and 80% (95% CI, 44-98), respectively.^9,10 
• A phase 2, single-arm study (NCT04965090) is evaluating the efficacy and safety of RYBREVANT plus lazertinib in patients with EGFR-mutated metastatic or recurrent NSCLC with progressive or new CNS metastases (brain metastases, n=20; leptomeninges, n=22) on previous treatment.^11,12 
  • For patients with brain metastases vs leptomeninges, systemic ORR was 30% (95% CI, 13-54) vs 33% (95% CI, 15-57), median PFS was 5.9 months (95% CI, 2.8-14.1) vs 8.3 months (95% CI, 3.3-12.2), and median OS was 17.9 months (95% CI, 15.4-not reached [NR]) vs 14.4 months (95% CI, 8-NR).¹² 
  • The most common (≥5%) grade ≥3 treatment-related adverse events (TRAEs) were infusion-related reactions (IRRs; 7%), thromboembolic events (5%), elevated aspartate transaminase/alanine transaminase (5%), and rash (5%). TRAEs leading to discontinuation of RYBREVANT were reported in 3 patients (7%).¹²
• PAPILLON (NCT04538664) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of RYBREVANT plus chemotherapy (carboplatin and pemetrexed; n=153) vs chemotherapy alone (carboplatin and pemetrexed; n=155) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon20ins mutations.^13,14
  • For patients with and without a history of brain metastases, the HR for the BICR-assessed PFS was 0.63 (95% CI, 0.38-1.06) and 0.33 (95% CI, 0.23-0.46), respectively, for RYBREVANT plus chemotherapy vs chemotherapy alone.¹⁴ 
• MARIPOSA-2 (NCT04988295) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of RYBREVANT-lazertinib-chemotherapy (pemetrexed and carboplatin; n=263) and RYBREVANT-chemotherapy (pemetrexed and carboplatin; n=131) vs chemotherapy alone (pemetrexed and carboplatin; n=263) in patients with EGFR-mutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC on or after osimertinib monotherapy.^15,16
  • For patients with a history of brain metastases, the HR for the BICR-assessed median PFS was 0.48 (95% CI, 0.34-0.67) for RYBREVANT-lazertinib-chemotherapy vs chemotherapy alone and 0.52 (95% CI, 0.35-0.78) for RYBREVANT-chemotherapy vs chemotherapy alone. For patients without a history of brain metastases, the HR for median PFS was 0.42 (95% CI, 0.31-0.58) for RYBREVANT-lazertinib-chemotherapy vs chemotherapy alone and 0.48 (95% CI, 0.33-0.7) for RYBREVANT-chemotherapy vs chemotherapy alone.^16,17 
• CHRYSALIS (NCT02609776) is an ongoing, phase 1, open-label, multicenter, dose-escalation and dose-expansion study evaluating the safety, efficacy, and PK of RYBREVANT as monotherapy and in combination with other therapies in adult patients with advanced NSCLC harboring EGFR mutations who had disease progression during or after previous SOC treatment.^18,19
  • Park et al (2021)¹⁹ reported results from cohort D of the CHRYSALIS study, which included patients with advanced NSCLC harboring Exon20ins mutations who received treatment with RYBREVANT at the recommended phase 2 dose (RP2D).
    • For patients with vs without a history of brain metastases, the BICR-assessed ORR was 45% vs 42%, and median OS was 19.9 months (95% CI, 14-NE) vs NE (95% CI, 18.5-NE).²⁰ 
• Safety was not separately evaluated for patients with brain metastases in the RYBREVANT studies summarized above, except in the phase 2, single-arm study.

PRODUCT LABELING

• RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.
• LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.

CLINICAL DATA

Combination with Lazertinib

MARIPOSA Study

Study Design/Methods

• Phase 3, ongoing, randomized study designed to assess the efficacy and safety of RYBREVANT plus lazertinib (open-label, n=429) vs osimertinib (double-blind, n=429) vs lazertinib (double-blind, n=216) as first-line treatment in 1074 patients with EGFRmutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC. The primary endpoint is BICR-assessed PFS for RYBREVANT plus lazertinib vs osimertinib.^2-4
  • RYBREVANT 1050 mg intravenous (IV; 1400 mg IV for body weight ≥80 kg) was administered every week (QW) for the first 4 weeks, with the initial dose as a split infusion on cycle (C) 1 day (D) 1 and D2, followed by every 2 weeks (Q2W) thereafter.
  • Lazertinib 240 mg was administered orally (PO) once daily.
  • Osimertinib 80 mg PO was administered once daily.
• All patients underwent scheduled magnetic resonance imaging (MRI) of the head at baseline, followed by subsequent scans every 8±1 weeks for the first 30 months, and then every 12 or 24±1 weeks until disease progression in patients with or without a history of brain metastases, respectively.⁴

Results

Patient Characteristics

• At baseline, 178 patients (41%) in the RYBREVANT plus lazertinib arm and 172 (40%) in the osimertinib arm had brain metastases.⁴

Efficacy

• The BICR-assessed median PFS (median follow-up, 22 months; data cutoff: August 11, 2023) and OS (median follow-up, 37.8 months; data cutoff: December 04, 2024) by brain metastases status reported as subgroup analyses in the MARIPOSA study are included in Table: MARIPOSA: Efficacy Outcomes by Brain Metastases Status. 

• At a median follow-up of 37.8 months (data cutoff: December 04, 2024), intracranial outcomes in patients with a history of brain metastases are included in Table: MARIPOSA: Intracranial Outcomes in Patients with a History of Brain Metastases.

Safety

• Median treatment duration was 27 months for RYBREVANT plus lazertinib and 22.4 months for osimertinib.⁵
• At the data cutoff date of December 04, 2024, no new safety signals were observed, with the first onset of most adverse events (AEs) occurring in the first 4 months.⁵
  • Most AEs were related to EGFR and MET inhibition and were grades 1-2 in severity.
  • Safety was not separately evaluated for patients with brain metastases.

CHRYSALIS-2 Study - Cohort A

Study Design/Methods

• Phase 1/1b, ongoing, open-label, multicenter, dose-escalation (phase 1) and dose-expansion (phase 1b) study designed to assess the efficacy, safety, PK, and immunogenicity of lazertinib as monotherapy and in combination with RYBREVANT in adult patients with metastatic or unresectable NSCLC harboring EGFR mutations (Exon19del or Exon 21 L858R, Exon20ins, or uncommon EGFR mutations) with disease progression on previous SOC treatment.⁶
• Cohort A included 162 patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced or metastatic NSCLC who received RYBREVANT plus lazertinib after prior treatment with osimertinib and platinum-based chemotherapy. The primary endpoint is investigator-accessed ORR.⁷ 
  • RYBREVANT 1050 mg IV (1400 mg IV for body weight ≥80 kg) QW for C1, with the initial dose as a split infusion on C1D1 and D2, followed by Q2W thereafter.
  • Lazertinib 240 mg PO was administered once daily.
• The study initially enrolled patients with stable or asymptomatic brain metastases treated or untreated. However, it was later amended to include only those who had completed definitive therapy for brain metastases to ensure a uniform CNS baseline status across all patients.⁷
• All patients underwent baseline brain imaging at screening, with subsequent brain imaging not mandatory for patients without brain metastases at baseline.⁷

Results

Patient Characteristics

• At baseline, 88 patients (54%) had a history of brain or CNS metastases or had brain or CNS lesions as target or nontarget lesions.⁷
• Among the 66 patients (41%) with baseline brain metastases identified on imaging, 29 (18%) had untreated brain metastases and 37 (23%) had received prior treatment.⁷

Efficacy

• At a median follow-up of 12.3 months (range, 0.3-27.2; data cutoff: November 15, 2022), the investigator-assessed ORR was 28% (95% CI, 22-36).⁷
• The BICR-assessed efficacy outcomes by brain metastases status reported as subgroup analyses in cohort A of the CHRYSALIS-2 study are included in Table: CHRYSALIS-2 (Cohort A): BICR-Assessed Efficacy Outcomes by Brain Metastases Status.

• Among the 66 patients (41%) with baseline brain metastases identified on imaging, 60 completed ≥1 postbaseline brain scan, of whom 17 (28%) showed an intracranial response. Among the 26 patients with untreated brain metastases (no previous brain radiation or surgery), 7 (27%) had investigator-assessed intracranial response.⁷
  • A patient with an untreated CNS lesion demonstrated intracranial response to RYBREVANT plus lazertinib on MRI at week 6, which was maintained through week 54.

Safety

• Median treatment duration was 4.6 months (range, 0.03-26.7).⁷
• Most treatment-emergent adverse events (TEAEs) were grade 1-2 in severity.⁷
• The most common TEAEs were rash (81%), IRR (68%), and paronychia (52%).⁷
• TRAEs led to discontinuation in 11 patients (7%), with IRRs being the most common cause (7 patients [4%]).⁷
• Safety was not separately evaluated for patients with brain metastases.

Phase 2 Single-Arm Study

Study Design/Methods

• Phase 2, ongoing, single-arm study designed to assess the efficacy and safety of RYBREVANT plus lazertinib in patients with EGFR-mutated metastatic or recurrent NSCLC with progressive or new CNS metastases (brain metastases, n=20; leptomeninges, n=22) on previous treatment. The coprimary endpoints are systemic ORR by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and CNS ORR by Response Assessment in Neuro-Oncology (RANO) criteria.^11,12
• Patients must have ≥1 measurable (≥5 mm) intracranial metastasis lesion.¹¹

Results

Patient Characteristics

• At baseline, patients with EGFR Exon19del (n=17), Exon 21 L858R (n=17), or atypical mutations (n=3) had received prior osimertinib and those with EGFR Exon20ins (n=5) had received prior chemotherapy.¹² 

Efficacy

• Efficacy outcomes in patients with CNS metastases are included in Table: Phase 2 Study: Efficacy Outcomes in Patients with Brain Metastases vs Leptomeninges.

• Among patients with leptomeninges with a median treatment time of 8.3 months (95% CI, 3.3-8.9), 14 patients (82%) reported a decreased number of circulating tumor cells in their cerebrospinal fluid and improvement in neurological symptoms.¹²

Safety

• Median treatment duration was 3.9 months (range, 0.3-18.6) for patients with brain metastases and 8.1 months (range, 0-21.7) for patients with leptomeninges.¹²
• The most common (≥30% in the overall population) TRAEs were rash (71%), IRR (59%), paronychia (43%), fatigue (40%), edema (40%), mucositis (33%), and nausea (33%).¹²
• The most common (≥5%) grade ≥3 TRAEs were IRRs (7%), thromboembolic events (5%), elevated aspartate transaminase/alanine transaminase (5%), and rash (5%).¹²
• TRAEs leading to discontinuation of RYBREVANT were reported in 3 patients (7%).¹²

Combination with Chemotherapy ± Lazertinib

PAPILLON Study

Study Design/Methods

• Phase 3, ongoing, randomized, open-label study designed to compare the efficacy and safety of RYBREVANT plus chemotherapy (carboplatin and pemetrexed; n=153) vs chemotherapy alone (carboplatin and pemetrexed; n=155) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon20ins mutations. The primary endpoint is BICR-assessed PFS.^13,14
  • RYBREVANT 1400 mg IV (1750 mg IV for body weight ≥80 kg) was administered QW for the first 4 weeks, with the initial dose as a split infusion on C1D1 and D2, followed by RYBREVANT 1750 mg IV (2100 mg IV for body weight ≥80 kg) every 3 weeks (Q3W) starting at week 7 (C3D1) until disease progression.
  • Pemetrexed 500 mg/m² IVwas administered Q3W until disease progression.
  • Carboplatin area under the curve (AUC) 5 IV was administered Q3W for up to 4 cycles.
• Patients with untreated brain metastases were excluded. Patients with asymptomatic or previously treated stable brain metastases were eligible only if they had discontinued corticosteroid treatment for ≥2 weeks prior to randomization.¹⁴

Results

Patient Characteristics

• At baseline, 35 patients (23%) in the RYBREVANT-chemotherapy arm and 36 (23%) in the chemotherapy alone arm had brain metastases.¹⁴

Efficacy

• At a median follow-up of 14.9 months, efficacy outcomes by brain metastases status reported as subgroup analyses in the PAPILLON study are included in Table: PAPILLON: BICR-Assessed Efficacy Outcomes by Brain Metastases Status.

Safety

• Median treatment duration was 9.7 months (range, 0.1-26.9) for RYBREVANT plus chemotherapy and 6.7 months (range, 0-25.3) for chemotherapy alone.¹⁴
• The most common (≥15% in either arm) AEs were neutropenia (59%), paronychia (56%), and rash (54%) for RYBREVANT plus chemotherapy and anemia (55%), neutropenia (45%), and nausea (42%) for chemotherapy alone.¹⁴
• Most patients in the study experienced ≥1 AE.¹⁴
• Safety was not separately evaluated for patients with brain metastases.

MARIPOSA-2 Study

Study Design/Methods

• Phase 3, ongoing, randomized, open-label study designed to assess the efficacy and safety of RYBREVANT-lazertinib-chemotherapy (n=263) and RYBREVANT-chemotherapy (n=131) vs chemotherapy alone (n=263) in 657 patients with EGFR-mutated locally advanced or metastatic NSCLC on or after osimertinib monotherapy (as the most recent line of therapy). The primary endpoint is BICR-assessed PFS.^15,16
  • RYBREVANT 1400 mg IV (1750 mg IV for body weight ≥80 kg) was administered QW for the first 4 weeks, with the initial dose as a split infusion on C1D1 and D2, followed by 1750 mg IV (2100 mg IV for body weight ≥80 kg) Q3W starting at week 7 (C3D1) until disease progression.
  • Lazertinib 240 mg PO was administered once daily.
  • Chemotherapy was administered Q3W at the beginning of each cycle, with carboplatin at AUC 5 IV for the first 4 cycles, and pemetrexed at 500 mg/m² IV until disease progression.
• In the RYBREVANT-lazertinib-chemotherapy arm, patients randomized before November 7, 2022, received lazertinib on C1D1. Due to an increase in hematologic and gastrointestinal toxicities in the arm, the regimen was modified to start lazertinib after carboplatin completion.¹⁶
  • An open-label, randomized, extension cohort will evaluate the efficacy and safety of the modified RYBREVANT-lazertinib-chemotherapy regimen vs RYBREVANT-chemotherapy.
• Patients with brain metastases were eligible if their intracranial disease was clinically stable and asymptomatic with stable doses of steroids and could receive ≤10 mg prednisone or equivalent daily for intracranial disease. Eligible patients did not require prior definitive local treatment with radiation or surgery, and any such treatment must have been completed ≥14 days prior to randomization.^15,16

Results

Patient Characteristics

• At baseline, 120 patients (46%) in the RYBREVANT-lazertinib-chemotherapy arm, 58 (44%) in the RYBREVANT-chemotherapy arm, and 120 (46%) in the chemotherapy alone arm had a history of brain metastases; of these, 56 patients (47%), 24 (41%), and 61 (51%), respectively, had not received prior brain radiation.¹⁶ 

Efficacy

• At a median follow-up of 8.7 months (data cutoff: July 10, 2023), the BICR-assessed median PFS by brain metastases status reported as subgroup analyses in the MARIPOSA-2 study are included in Table: MARIPOSA-2: BICR-Assessed Efficacy Outcomes by Brain Metastases Status.

• The BICR-assessed intracranial PFS (icPFS) by brain metastases status reported as subgroup analyses in the MARIPOSA-2 study are included in Table: MARIPOSA-2: BICR-Assessed Intracranial Outcomes by Brain Metastases Status.

Safety

• The rates of grade ≥3 AEs were 92% (n=242) for RYBREVANT-lazertinib-chemotherapy, 72% (n=94) for RYBREVANT-chemotherapy, and 48% (n=117) for chemotherapy alone.¹⁶
• The most common (≥10% in any arm) grade ≥3 AEs were neutropenia, thrombocytopenia, anemia, and leukopenia.¹⁶
• TRAEs leading to death occurred in 4 (2%), 2 (2%), and 1 (0.4%) patient(s) in the RYBREVANT-lazertinib-chemotherapy, RYBREVANT-chemotherapy, and chemotherapy alone arms, respectively.¹⁶
• Safety was not separately evaluated for patients with brain metastases.

CHRYSALIS-2 Study - LACP Cohort

Study Design/Methods

• Phase 1/1b, ongoing, open-label, multicenter, dose-escalation (phase 1) and dose-expansion (phase 1b) study designed to assess the efficacy, safety, PK, and immunogenicity of lazertinib as monotherapy and in combination with RYBREVANT in adult patients with metastatic or unresectable NSCLC harboring EGFR mutations (Exon19del or Exon 21 L858R, Exon20ins, or uncommon EGFR mutations) with disease progression on previous SOC treatment.⁶
• The LACP cohort included 20 patients with EGFR-mutated advanced NSCLC post-TKI (maximum 3 prior lines of therapy) who received RYBREVANT-lazertinib-chemotherapy (pemetrexed and carboplatin). The primary endpoint is safety.⁹
  • RYBREVANT 1400 mg IV (1750 mg IV for body weight ≥80 kg) was administered QW for the first 4 weeks, with the initial dose as a split infusion on C1D1 and D2, followed by RYBREVANT 1750 mg IV (2100 mg IV for body weight ≥80 kg) Q3W starting C3D1 until disease progression.
  • Carboplatin AUC 5 IV was administered Q3W for up to 4 cycles.
  • Pemetrexed 500 mg/m² IVwas administered Q3W until disease progression.
  • Lazertinib 240 mg PO was administered once daily.

Results

Patient Characteristics

• At baseline, 12 patients (60%) in the LACP cohort had brain metastases.⁹

Efficacy

• Efficacy outcomes in a subgroup of patients with brain metastases are included in Table: CHRYSALIS-2 Study (LACP Cohort): Investigator-Assessed Efficacy in Patients with a History of Brain Metastases.

Safety

• At a median follow-up of 13.1 months (data cutoff: November 15, 2022), median number of treatment cycles was 15.5 (range, 2-23).⁹
• The safety profile was consistent with that of the individual components, with no new safety signals identified.⁹
  • AEs were mostly grade 1-2 in severity.
  • The most common (≥20%) AEs were neutropenia (90%), IRR (65%), fatigue (50%), and nausea (50%).
• Safety was not separately evaluated for patients with brain metastases.

Single-Agent RYBREVANT

CHRYSALIS Study - Cohort D

Study Design/Methods

• Phase 1, ongoing, open-label, multicenter, dose-escalation and dose-expansion study designed to assess the safety, efficacy, and PK of RYBREVANT as monotherapy and in combination with other therapies in adult patients with advanced NSCLC harboring EGFR mutations who had disease progression during or after previous SOC treatment.^18,19
• Cohort D included 114 patients with metastatic or unresectable advanced NSCLC harboring Exon20ins mutations with disease progression during or after platinum-based chemotherapy who received treatment with RYBREVANT as monotherapy at the RP2D. The primary endpoints are dose-limiting toxicity incidence (dose escalation) and ORR assessed per RECIST v1.1 (dose expansion).¹⁹
  • RYBREVANT monotherapy was administered at the RP2D: 1050 mg IV (1400 mg IV for body weight ≥80 kg) QW for C1, with the initial dose as a split infusion on C1D1 and D2, and Q2W thereafter until disease progression or unacceptable toxicity.
  • Patients with untreated or active brain metastases were excluded; however, patients whose brain metastases were previously treated and asymptomatic at screening were eligible.

Results

Patient Characteristics

• At baseline, 18 patients (22%) in cohort D had brain metastases.¹⁹

Efficacy

• At a median follow-up of 9.7 months (range, 1.1-29.3; data cutoff: October 8, 2020), the BICR-assessed ORR in the primary analysis (n=81) was 40% (95% CI, 29-51).¹⁹
  • In a subgroup analysis by brain metastasis status, ORRs were 39% (95% CI, 17-64; n/N=7/18) in patients with a history of brain metastases and 40% (95% CI, 28-53; n/N=25/63) in patients without a history of brain metastases at baseline.
• At a median follow-up of 12.5 months (range, 0.2-30.5), 31.6% of patients with brain metastases (n=38) and 6.6% without brain metastases (n=76) at baseline experienced first investigator-assessed progressive disease in the brain.²⁰
  • Efficacy outcomes by brain metastases status reported as subgroup analyses in cohort D of the CHRYSALIS study are included in Table: CHRYSALIS (Cohort D): Efficacy Outcomes by Brain Metastases Status.

Safety

• At a median follow-up of 5.1 months (range, 0.2-29.3), AEs were mostly grade 1-2 in severity (grade ≥3, 35%).¹⁹
• AEs leading to treatment discontinuations included rash (1.8%; n=2), IRRs (1.8%; n=2), and paronychia (1%; n=1).¹⁹
• Safety was not separately evaluated for patients with brain metastases.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources including internal/external databases) was conducted on 19 May 2025.