1269P - Preventing infusion-related reactions with intravenous amivantamab: Updated results from SKIPPirr, a phase II study

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Intravenous (IV) ami has an infusion-related reaction (IRR) incidence of ∼67%, typically at first infusion. The phase 2 SKIPPirr study evaluated prophylactic strategies to reduce the incidence and severity of IRRs.

Methods

SKIPPirr (NCT05663866) enrolled patients (pts) with EGFR-mutated (Ex19del or L858R) advanced NSCLC after progression on sequential osimertinib and platinum-based chemo. All pts received IV ami and oral (PO) lazertinib (laz), a 3^rd gen EGFR TKI. Four prophylactic approaches were evaluated: 4-mg PO dexamethasone (dex) twice daily (BID) on cycle (C) 1 day (D)-1; 8-mg PO dex BID on C1D-2 and C1D-1 and 8-mg PO 1 hour (h) before infusion; 10-mg PO montelukast once daily from C1D-4 to C1D1; and 25-mg subcutaneous methotrexate as a single dose between C1D-7 and C1D-3. Primary endpoint was IRR incidence at C1D1. A Simon’s two-stage design was used for each cohort individually. Stage 1 enrolled up to 6 pts/cohort and was stopped if 4 or more pts had IRRs at C1D1. Stage 2 enrolled up to 10 additional pts and was stopped if 9 or more pts (including Stage 1) had IRRs at C1D1. Expansion stage enrolled up to 24 additional pts.

Results

As of 8 Mar 2024, 65 pts were enrolled (median follow-up: 3.2 months). Median age was 63 years, 65% were female, and 63% Asian, with a median of 3 prior lines of treatment. Only the 8-mg dex cohort passed stages 1 and 2 (2/6 and 6/16 pts with IRR), enrolling 22 more pts until data cutoff (1 pt did not receive prophylaxis per protocol and was excluded from efficacy analyses). At clinical cutoff, 9/37 pts (24%) had IRRs at C1D1 (all grade ≤2). Median infusion time was 5.5 h for pts with IRR vs 4.4 h for pts without. Since data cutoff, 3 additional pts have been enrolled. The full dataset with secondary endpoints will be reported at the congress. The most common IRR-related symptoms were dyspnea (26%), hypotension (21%), and nausea (21%), mostly grade 1-2. No pt discontinued ami-laz due to IRRs. Among 24 response-evaluable pts, 9 (38%) had a partial response, similar to prior reports in this population.

Conclusions

Prophylaxis with 8-mg PO dex effectively reduces ami-related IRRs, with a meaningful IRR reduction compared to historical IV data.

Clinical trial identification

NCT05663866.

Editorial acknowledgement

Medical writing assistance was provided by Claire E. Brady, PharmD, of Lumanity Communications Inc and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Global Services LLC.

Disclosure

L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati, Boehringer; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of CancerResearch): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group; Non-Financial Interests, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Leadership Role, President: Oncosur Foundation. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma. J. Han: Financial Interests, Personal, Advisory Board: Norvatis, Lantern, Takeda, Janssen, Merck, Pfizer, Amgen, AstraZeneca, Oncobix, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, Jassen, Merck, Roche, Yuhan, Pfizer, Norvatis. J. Shih: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Ono Pharmaceutical, Takeda, CStone Pharmaceuticals, Janssen, and Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Ono Pharmaceutical, and Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Roche. C. Mascaux: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, Kephren, Janssens, Takeda, Sanofi, Novartis. U. Basu Roy: Financial Interests, Institutional, Speaker, Consultant, Advisor: Janssen. J. Zugazagoitia: Financial Interests, Personal, Research Grant: AstraZeneca, Roche, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Sanofi, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Janssen, Takeda, Sanofi, Roche, AstraZeneca, NanoString, Amgen, BMS, Pfizer, MSD, Diagnostica Longwood; Financial Interests, Personal, Other, Attending meetings and/or travel: Janssen, Sanofi, AstraZeneca, Takeda, Roche. C.H. Chiu: Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Shionogi, and Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Merck KGaA, Novartis, Ono Pharmaceutical, Roche. S. Kim: Financial Interests, Personal, Other: Provision of study material Medical Writing. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi Sankyo, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Pfizer, Roche, Apollomics, Transgene; Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). I. Gil Bazo: Financial Interests, Personal, Speaker, Consultant, Advisor: Johnson & Johnson, Lilly, Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria for lectures: Johnson & Johnson, Amgen, AstraZeneca, MSD, Takeda; Financial Interests, Personal, Other, Attending meetings and/or travel: Johnson & Johnson, MSD, Daiichi Sankyo, Sanofi. P. Mahadevia, B. Anderson, K. Xia, G. Wang, J.M. Bauml, M. Chioda, J. Simões: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. G. Lopes: Financial Interests, Personal, Stocks or ownership: Lucence Diagnostics, Xilis, Biomad, Morphometrix, CDR-Life; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Blueprint Medicines, AstraZeneca, Merck, Janssen; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, AstraZeneca; Financial Interests, Personal and Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Research Funding: Lucence, Xilis, E.R. Squibb Sons, LLC, Merck Sharp & Dohme, EMD Serono; Financial Interests, Institutional, Research Funding: Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, BMS, GSK, AbbVie, Rgenix, Pfizer, Lilly, Janssen; Financial Interests, Personal, Other, Travel: Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen, Seattle Genetics, Celgene, Ibsen, Pharmacyclics, AstraZeneca, Seagen; Financial Interests, Personal, Other: Mirati Therapeutics. All other authors have declared no conflicts of interest.