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PALOMA-3

Lung Cancer

PALOMA-3

Manufactured by: Johnson & Johnson (Janssen Pharmaceuticals)
Product name: Rybrevant® (Amivantamab)

About the PALOMA-3 Trial

The PALOMA-3 trial is a Phase 3 study comparing subcutaneous (SC) versus intravenous (IV) administration of amivantamab in combination with lazertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The primary endpoint was overall response rate (ORR), with secondary endpoints including duration of response (DoR) and overall survival (OS). The study demonstrated comparable ORR between SC and IV administration arms, but the SC formulation offered meaningful advantages, including fewer infusion-related reactions and improved patient convenience. Notably, the SC arm showed a longer DoR (11.2 months vs. 8.3 months with IV). These findings were presented at the 2024 ASCO Annual Meeting, with expert commentary provided by Dr. Chul Kim.

Table of Contents

Major Presentations and Milestones

PALOMA-3 Trial design, results, and conclusions

PALOMA-3 Sentiments and Criticisms

PALOMA-3 Temporal Sentiment Arc

Professional Resources : Interactive Tweet History, Influence Diagram, Sentiment Table, AI Chatbot


FDA Approved

FDA Approval Announcement

PALOMA-3 Trial: Major Presentations and Milestones

Primary speakers driving the story

At ASCO 2024 (May 31, 2024), Natasha Leighl, MD (Princess Margaret Cancer Centre) presented the phase 3 PALOMA-3 primary results comparing subcutaneous (SC) versus intravenous (IV) amivantamab, each given with lazertinib, in previously treated EGFR-mutated advanced NSCLC. KOL coverage emphasized the noninferior pharmacokinetics of SC dosing, similar response rates, an exploratory OS advantage for SC administration, and substantially fewer infusion reactions with SC.

Eric K. Singhi, MD (ASCO24): "Dr. Natasha Leighl now reviews data from the PALOMA-3 Trial at #ASCO24 Very excited to hear about this data regarding subcutaneous amivantamab-- a real potential to transform the current patient experience with this drug"

Sanjay Popat, MD (ASCO24): "PK non-inferiority endpoints met. ORR non inferior. DOR and PFS and OS (sign) improved for SC. TRAEs similar between arms. Marked reduction in IRRs"

Charu Aggarwal, MD, MPH, FASCO (ASCO24): "SC administration wins over IV and reduces burden on patients by reducing adelverse events (toxicity), time toxicity and financial toxicity"

PALOMA-3 Trial Design, Results, and Conclusions

Trial Design:

PALOMA-3 is a phase 3 study in advanced EGFR-mutated NSCLC patients treated after osimertinib and platinum chemotherapy (third-line setting). Patients were randomized to subcutaneous (SC) or intravenous (IV) amivantamab, each with lazertinib. The prespecified primary objective was noninferiority of SC versus IV pharmacokinetics. Key efficacy endpoints included ORR (noninferiority), and time-to-event outcomes (DOR, PFS, OS); OS analysis was exploratory (nominal p-values, not in hierarchical testing).

Primary Results:

- Pharmacokinetics: Noninferiority achieved for SC amivantamab versus IV (per protocol PK endpoints). ORR was noninferior (approximately 30% SC vs 33% IV; confirmed ORR 27% vs 27%). Duration of response favored SC (median 11.2 months vs 8.3 months in IV, per on-slide data shared by KOLs).

- Survival: An exploratory OS analysis favored SC over IV (HR 0.62; 95% CI 0.42–0.92; nominal p=0.02). PFS was numerically better with SC but not statistically significant in the reported analysis (HR ~0.84; not significant).

- Safety: SC administration markedly reduced infusion-related reactions (IRRs). One KOL summarized IRRs as 13% with SC versus 66% with IV, with milder symptoms in the SC arm; venous thromboembolism (VTE) events were less common with SC regardless of prophylaxis status. Discontinuation and dose-reduction rates were similar between arms in session commentary.

Key Conclusions:

In previously treated EGFR-mutated advanced NSCLC, SC amivantamab (with lazertinib) achieved PK noninferiority to IV dosing, similar ORR, longer DOR, and an exploratory OS benefit versus IV, with substantially fewer IRRs and no clear loss of dose intensity. PFS was not significantly different in the reported analysis. KOLs emphasized operational advantages of SC delivery (reduced chair time, fewer IRRs) and raised mechanistic questions (e.g., lymphatic exposure, anti-drug antibodies) that may warrant further study.

PALOMA-3 Sentiments and Criticisms

Positive Reception:

Chul Kim, MD: "Similar ORRs, numerically better PFS, improved OS with SC vs. IV. Significant reduction in IRRs with SC vs. IV (shorter administration time as well)! A great option for patients." https://x.com/chulkimMD/status/1796653651211010089

Charu Aggarwal, MD, MPH, FASCO: "SC administration wins over IV and reduces burden on patients by reducing adelverse events (toxicity), time toxicity and financial toxicity" https://x.com/CharuAggarwalMD/status/1796657250787795333

Sanjay Popat, MD: "PK non-inferiority endpoints met. ORR non inferior. DOR and PFS and OS (sign) improved for SC. ... Marked reduction in IRRs" https://x.com/DrSanjayPopat/status/1796653027345981816

Critical Perspectives:

Stephen V Liu, MD underscored hierarchy and interpretation: "#ASCO24 Exploratory OS analysis favors SQ amivantamab over IV route with OS HR 0.62 - exploratory but very intriguing! Differences in clearance? Immune mechanism involving lymphatic exposure?" https://x.com/StephenVLiu/status/1796652865898881481

Benjamin Besse, MD queried immunogenicity: "Are blocking ADAs (anti drug antibodies) more frequent with IV vs S/C?" https://x.com/BenjaminBesseMD/status/1796657366747754845

Tom Newsom‑Davis, MD highlighted the pattern of effects and practical parity in discontinuation/dose reduction while positing potential biological explanations.

PALOMA-3 Temporal Sentiment Arc

2024 (ASCO24 primary results)

Primary/KOL tweets:

Late 2024 (Post-conference reflections and education)

Primary/KOL tweets:

Overall, the discourse coalesced around maintaining efficacy with SC dosing while materially reducing infusion burden and IRRs, acknowledging that the OS finding is exploratory and hypothesis‑generating.

PALOMA-3 Professional Resources