A New Pre­ci­sion Ap­proach for Non-Small Cell Lung Can­cer with EGFR Ex­on 20 In­ser­tion Mu­ta­tions

Lung can­cer is the world’s lead­ing cause of death due to can­cer ac­cord­ing to the World Health Or­ga­ni­za­tion.¹ Thus an ur­gent and im­mense un­met need re­mains for new and ef­fec­tive treat­ments —es­pe­cial­ly for peo­ple af­fect­ed by non-small cell lung can­cer (NSCLC), or about 80 to 85% of lung can­cer di­ag­noses.² At John­son & John­son, we are work­ing to meet this need with in­no­v­a­tive treat­ments, a pa­tient-cen­tric re­search ap­proach dri­ven by pre­ci­sion, and sin­gu­lar fo­cus to get in front of can­cer and help trans­form the lives of peo­ple fac­ing a lung can­cer di­ag­no­sis.

Why Nov­el Mech­a­nisms of Ac­tion and a New Treat­ment Land­scape Are Need­ed for NSCLC with Ex­on20 In­ser­tion Mu­ta­tions

Many ge­net­ic mu­ta­tions can con­tribute to tu­mor de­vel­op­ment, but al­ter­ations in the epi­der­mal growth fac­tor re­cep­tor (EGFR), a re­cep­tor ty­ro­sine ki­nase con­trol­ling cell growth and di­vi­sion, are among the most com­mon dri­ver mu­ta­tions in NSCLC.³ EGFR mu­ta­tions have been ob­served in up to 15% of NSCLC ade­no­car­ci­no­mas across the broad­er pop­u­la­tion, with this preva­lence in­creas­ing to be­tween 22% and 26% in North Amer­i­ca.^4,5 While over­all they are rare, EGFR ex­on 20 in­ser­tions con­sti­tute 12% of all EGFR mu­ta­tion types.⁶

Pa­tients with EGFR ex­on 20 in­ser­tion mu­ta­tions have a worse prog­no­sis than those with EGFR TKI-sen­si­tive mu­ta­tions.⁷ Giv­en the ten­den­cy for rapid dis­ease pro­gres­sion among these pa­tients, there is a dire need for first-line tar­get­ed ap­proach­es.

With a fo­cus on sci­en­tif­ic ex­cel­lence and in­no­va­tion dri­ven by our am­bi­tion to help trans­form pa­tient out­comes, we’ve ded­i­cat­ed our world-class re­search ca­pa­bil­i­ties to bring­ing for­ward dif­fer­en­ti­at­ed, im­mune-dri­ven mech­a­nisms of ac­tion and in­tro­duc­ing new treat­ment op­tions for pa­tients with EGFR-mu­tat­ed NSCLC.

A Per­son­al­ized Treat­ment Op­tion in NSCLC with EGFR Ex­on20 In­ser­tion Mu­ta­tions

Pre­ci­sion med­i­cine and its po­ten­tial to trans­form health­care de­liv­ery is a core fo­cus for John­son & John­son On­col­o­gy as we work to achieve mean­ing­ful change for pa­tients, and it’s be­come a foun­da­tion­al el­e­ment of our strat­e­gy to­wards tar­get­ed ther­a­pies tai­lored to a per­son’s unique case based on patho­log­ic find­ings, clin­i­cal stag­ing, and mol­e­c­u­lar pro­fil­ing.

One such ex­am­ple of our com­mit­ment to NSCLC pa­tients is the re­cent U.S. Food and Drug Ad­min­is­tra­tion (FDA) ap­proval of RY­BRE­VANT^® (ami­van­tam­ab-vmjw) in com­bi­na­tion with car­bo­platin and peme­trexed (chemother­a­py) for the first-line treat­ment of adult pa­tients with lo­cal­ly ad­vanced or metasta­t­ic NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions as de­tect­ed by an FDA-ap­proved test. This mile­stone rep­re­sents a sig­nif­i­cant step for­ward in how we’re work­ing to­wards our vi­sion to change the stan­dard of care and re­shape the over­all treat­ment land­scape for peo­ple af­fect­ed by lung can­cer.

RY­BRE­VANT^® is a ful­ly-hu­man bis­pe­cif­ic an­ti­body di­rect­ed against EGFR and MET re­cep­tors.⁸ Com­bin­ing RY­BRE­VANT^®-dri­ven im­mune cell ac­ti­va­tion with chemother­a­py-me­di­at­ed cell death may have com­pli­men­ta­ry an­ti­tu­mor ac­tiv­i­ty.⁹

This re­cent ap­proval is based on pos­i­tive re­sults from the ran­dom­ized, open-la­bel Phase 3 PA­PIL­LON study, which showed RY­BRE­VANT^® plus chemother­a­py re­sult­ed in a 60% (Haz­ard Ra­tio [HR]=0.40; 95 per­cent Con­fi­dence In­ter­val [CI], 0.30–0.53; p val­ue P<0.0001) re­duc­tion in the risk of dis­ease pro­gres­sion or death com­pared to chemother­a­py alone.⁸ In PA­PIL­LON, in­ves­ti­ga­tors al­so stud­ied the im­pact of treat­ment with RY­BRE­VANT^® plus chemother­a­py on over­all re­sponse rate (ORR).⁸ The most com­mon ad­verse re­ac­tions in PA­PIL­LON with RY­BRE­VANT^® and chemother­a­py (≥20 per­cent) were rash, nail tox­i­c­i­ty, stom­ati­tis, IRR, fa­tigue, ede­ma, con­sti­pa­tion, de­creased ap­petite, nau­sea, COVID-19, di­ar­rhea and vom­it­ing.⁸

Based on PA­PIL­LON da­ta, the Na­tion­al Can­cer Com­pre­hen­sive Net­work^® (NC­CN^®) up­dat­ed its NC­CN Clin­i­cal Prac­tice Guide­lines in On­col­o­gy (NC­CN Guide­lines^®) to in­clude a NC­CN Cat­e­go­ry 1 rec­om­men­da­tion for ami­van­tam­ab-vmjw (RY­BRE­VANT^®) plus chemother­a­py as a pre­ferred first-line ther­a­py op­tion for pa­tients with non­squa­mous mN­SCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions.¹⁰

The cur­rent FDA ap­proval for RY­BRE­VANT^® plus chemother­a­py marks de­liv­ery of the first and on­ly tar­get­ed treat­ment for adult pa­tients with NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions ap­proved for first-line.⁸ By in­tro­duc­ing new ap­proach­es such as this, we aim to pro­vide new op­tions for pa­tients with NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions—a mu­ta­tion type known to car­ry a worse prog­no­sis com­pared with lung can­cer dri­ven by oth­er EGFR mu­ta­tions¹¹—and to ad­vance tar­get­ed ther­a­py op­tions tai­lored to in­di­vid­ual pa­tient needs.

 De­vel­op­ing a Trans­for­ma­tive Lung Can­cer Port­fo­lio

Each treat­ment break­through pro­vides an im­por­tant new op­tion for pa­tients and fam­i­lies who are count­ing on us to ad­vance the sci­ence and win the bat­tle against can­cer. Across our ground­break­ing work at J&J On­col­o­gy, we’re un­der­tak­ing a mul­ti-pronged sci­en­tif­ic ap­proach to tar­get the com­plex na­ture of lung can­cer, ad­vanc­ing tar­get­ed treat­ment ap­proach­es and en­hanc­ing ac­cess to per­son­al­ized ther­a­pies for more pa­tients who need them. With this re­cent ap­proval and the po­ten­tial to in­tro­duce mul­ti­ple con­tin­ued stud­ies for RY­BRE­VANT^®, both as a monother­a­py and in com­bi­na­tion reg­i­mens, we be­lieve we are on­ly at the be­gin­ning of what we can achieve in our pur­suit of cre­at­ing a new treat­ment land­scape for NSCLC.

Learn more about how John­son & John­son is work­ing to­wards a world free of can­cer at https://www.ry­bre­van­thcp.com/.

*See the NC­CN Guide­lines^® for de­tailed rec­om­men­da­tions, in­clud­ing oth­er treat­ment op­tions. The NC­CN Guide­lines for NSCLC pro­vide rec­om­men­da­tions for cer­tain in­di­vid­ual bio­mark­ers that should be test­ed and rec­om­mend test­ing tech­niques but do not en­dorse any spe­cif­ic com­mer­cial­ly avail­able bio­mark­er as­says or com­mer­cial lab­o­ra­to­ries. The NC­CN Con­tent does not con­sti­tute med­ical ad­vice and should not be used in place of seek­ing pro­fes­sion­al med­ical ad­vice, di­ag­no­sis or treat­ment by li­censed prac­ti­tion­ers. NC­CN makes no war­ranties of any kind what­so­ev­er re­gard­ing their con­tent, use or ap­pli­ca­tion and dis­claims any re­spon­si­bil­i­ty for their ap­pli­ca­tion or use in any way.

RY­BRE­VANT^® IM­POR­TANT SAFE­TY IN­FOR­MA­TION⁹

IN­DI­CA­TIONS

RY­BRE­VANT^® (ami­van­tam­ab-vmjw) is in­di­cat­ed in com­bi­na­tion with car­bo­platin and peme­trexed for the first-line treat­ment of adult pa­tients with lo­cal­ly ad­vanced or metasta­t­ic non-small cell lung can­cer (NSCLC) with epi­der­mal growth fac­tor re­cep­tor (EGFR) ex­on 20 in­ser­tion mu­ta­tions, as de­tect­ed by an FDA-ap­proved test.

RY­BRE­VANT^® (ami­van­tam­ab-vmjw) is in­di­cat­ed as a sin­gle agent for the treat­ment of adult pa­tients with lo­cal­ly ad­vanced or metasta­t­ic NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions, as de­tect­ed by an FDA-ap­proved test, whose dis­ease has pro­gressed on or af­ter plat­inum-based chemother­a­py.

IM­POR­TANT SAFE­TY IN­FOR­MA­TION

WARN­INGS AND PRE­CAU­TIONS

The safe­ty pop­u­la­tion of RY­BRE­VANT^® with car­bo­platin and peme­trexed de­scribed in Warn­ings and Pre­cau­tions was based on 151 pa­tients in the PA­PIL­LON study.

The safe­ty pop­u­la­tion of RY­BRE­VANT^® as a sin­gle agent de­scribed in Warn­ings and Pre­cau­tions was based on 129 pa­tients in the CHRYSALIS study.

In­fu­sion-Re­lat­ed Re­ac­tions

RY­BRE­VANT^® can cause in­fu­sion-re­lat­ed re­ac­tions (IRR); signs and symp­toms of IRR in­clude dys­p­nea, flush­ing, fever, chills, nau­sea, chest dis­com­fort, hy­poten­sion, and vom­it­ing.

RY­BRE­VANT^® with Car­bo­platin and Peme­trexed

RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed can cause in­fu­sion-re­lat­ed re­ac­tions. Based on the safe­ty pop­u­la­tion, in­fu­sion-re­lat­ed re­ac­tions oc­curred in 42% of pa­tients treat­ed with RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed, in­clud­ing Grade 3 (1.3%) ad­verse re­ac­tions. The in­ci­dence of in­fu­sion mod­i­fi­ca­tions due to IRR was 40%, and 0.7% of pa­tients per­ma­nent­ly dis­con­tin­ued RY­BRE­VANT^®.

RY­BRE­VANT^® as a Sin­gle Agent

Based on the safe­ty pop­u­la­tion, IRR oc­curred in 66% of pa­tients treat­ed with RY­BRE­VANT^®. Among pa­tients re­ceiv­ing treat­ment on Week 1 Day 1, 65% ex­pe­ri­enced an IRR, while the in­ci­dence of IRR was 3.4% with the Day 2 in­fu­sion, 0.4% with the Week 2 in­fu­sion, and cu­mu­la­tive­ly 1.1% with sub­se­quent in­fu­sions. Of the re­port­ed IR­Rs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The me­di­an time to on­set was 1 hour (range 0.1 to 18 hours) af­ter start of in­fu­sion. The in­ci­dence of in­fu­sion mod­i­fi­ca­tions due to IRR was 62% and 1.3% of pa­tients per­ma­nent­ly dis­con­tin­ued RY­BRE­VANT^® due to IRR.

Pre­med­icate with an­ti­his­t­a­mines, an­tipyret­ics, and glu­co­cor­ti­coids and in­fuse RY­BRE­VANT^® as rec­om­mend­ed. Ad­min­is­ter RY­BRE­VANT^® via a pe­riph­er­al line on Week 1 and Week 2. Mon­i­tor pa­tients for any signs and symp­toms of in­fu­sion re­ac­tions dur­ing RY­BRE­VANT^® in­fu­sion in a set­ting where car­diopul­monary re­sus­ci­ta­tion med­ica­tion and equip­ment are avail­able. In­ter­rupt in­fu­sion if IRR is sus­pect­ed. Re­duce the in­fu­sion rate or per­ma­nent­ly dis­con­tin­ue RY­BRE­VANT^® based on sever­i­ty.

In­ter­sti­tial Lung Dis­ease/Pneu­moni­tis

RY­BRE­VANT^® can cause in­ter­sti­tial lung dis­ease (ILD)/pneu­moni­tis.

RY­BRE­VANT^® with Car­bo­platin and Peme­trexed

Based on the safe­ty pop­u­la­tion, Grade 3 ILD/pneu­moni­tis oc­curred in 2.6% of pa­tients treat­ed with RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed. All pa­tients re­quired per­ma­nent dis­con­tin­u­a­tion.

RY­BRE­VANT^® as a Sin­gle Agent

Based on the safe­ty pop­u­la­tion, ILD/pneu­moni­tis oc­curred in 3.3% of pa­tients treat­ed with RY­BRE­VANT^®, with 0.7% of pa­tients ex­pe­ri­enc­ing Grade 3 ILD/pneu­moni­tis. Three pa­tients (1%) dis­con­tin­ued RY­BRE­VANT^® due to ILD/pneu­moni­tis.

Mon­i­tor pa­tients for new or wors­en­ing symp­toms in­dica­tive of ILD/pneu­moni­tis (e.g., dys­p­nea, cough, fever). Im­me­di­ate­ly with­hold RY­BRE­VANT^® in pa­tients with sus­pect­ed ILD/pneu­moni­tis and per­ma­nent­ly dis­con­tin­ue if ILD/pneu­moni­tis is con­firmed.

Der­ma­to­log­ic Ad­verse Re­ac­tions

RY­BRE­VANT^® can cause rash (in­clud­ing der­mati­tis ac­neiform), pru­ri­tus and dry skin.

RY­BRE­VANT^® with Car­bo­platin and Peme­trexed

RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed can cause der­ma­to­log­ic ad­verse re­ac­tions. Based on the safe­ty pop­u­la­tion, rash oc­curred in 89% of pa­tients treat­ed with RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed, in­clud­ing Grade 3 (19%) ad­verse re­ac­tions. Rash lead­ing to dose re­duc­tions oc­curred in 19% of pa­tients, and 2% per­ma­nent­ly dis­con­tin­ued RY­BRE­VANT^®, and 1.3% dis­con­tin­ued peme­trexed.

RY­BRE­VANT^® as a Sin­gle Agent

Based on the safe­ty pop­u­la­tion, rash oc­curred in 74% of pa­tients treat­ed with RY­BRE­VANT^®, in­clud­ing Grade 3 rash in 3.3% of pa­tients. The me­di­an time to on­set of rash was 14 days (range: 1 to 276 days). Rash lead­ing to dose re­duc­tion oc­curred in 5% of pa­tients, and RY­BRE­VANT^® was per­ma­nent­ly dis­con­tin­ued due to rash in 0.7% of pa­tients.

Tox­ic epi­der­mal necrol­y­sis oc­curred in one pa­tient (0.3%) treat­ed with RY­BRE­VANT^® as a sin­gle agent.

In­struct pa­tients to lim­it sun ex­po­sure dur­ing and for 2 months af­ter treat­ment with RY­BRE­VANT^®. Ad­vise pa­tients to wear pro­tec­tive cloth­ing and use broad-spec­trum UVA/UVB sun­screen. Al­co­hol‑free emol­lient cream is rec­om­mend­ed for dry skin.

If skin re­ac­tions de­vel­op, start top­i­cal cor­ti­cos­teroids and top­i­cal and/or oral an­tibi­otics. For Grade 3 re­ac­tions, add oral steroids and con­sid­er der­ma­to­log­ic con­sul­ta­tion. Prompt­ly re­fer pa­tients pre­sent­ing with se­vere rash, atyp­i­cal ap­pear­ance or dis­tri­b­u­tion, or lack of im­prove­ment with­in 2 weeks to a der­ma­tol­o­gist. With­hold, dose re­duce or per­ma­nent­ly dis­con­tin­ue RY­BRE­VANT^® based on sever­i­ty.

Oc­u­lar Tox­i­c­i­ty

RY­BRE­VANT^® can cause oc­u­lar tox­i­c­i­ty in­clud­ing ker­ati­tis, dry eye symp­toms, con­junc­ti­val red­ness, blurred vi­sion, vi­su­al im­pair­ment, oc­u­lar itch­ing, and uveitis.

RY­BRE­VANT^® with Car­bo­platin and Peme­trexed

Based on the safe­ty pop­u­la­tion, RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed can cause oc­u­lar tox­i­c­i­ty in­clud­ing ble­phar­i­tis, dry eye, con­junc­ti­val red­ness, blurred vi­sion, and eye pru­ri­tus. All events were Grade 1-2.

RY­BRE­VANT^® as a Sin­gle Agent

Based on the safe­ty pop­u­la­tion, ker­ati­tis oc­curred in 0.7% and uveitis oc­curred in 0.3% of pa­tients treat­ed with RY­BRE­VANT^®. All events were Grade 1-2. Prompt­ly re­fer pa­tients pre­sent­ing with eye symp­toms to an oph­thal­mol­o­gist. With­hold, dose re­duce or per­ma­nent­ly dis­con­tin­ue RY­BRE­VANT^® based on sever­i­ty.

Em­bryo-Fe­tal Tox­i­c­i­ty

Based on its mech­a­nism of ac­tion and find­ings from an­i­mal mod­els, RY­BRE­VANT^® can cause fe­tal harm when ad­min­is­tered to a preg­nant woman. Ad­vise fe­males of re­pro­duc­tive po­ten­tial of the po­ten­tial risk to the fe­tus. Ad­vise fe­male pa­tients of re­pro­duc­tive po­ten­tial to use ef­fec­tive con­tra­cep­tion dur­ing treat­ment and for 3 months af­ter the last dose of RY­BRE­VANT^®.

Ad­verse Re­ac­tions

RY­BRE­VANT^® with Car­bo­platin and Peme­trexed

For the 151 pa­tients in the PA­PIL­LON clin­i­cal tri­al who re­ceived RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed, the most com­mon ad­verse re­ac­tions (≥20%) were rash (90%), nail tox­i­c­i­ty (62%), stom­ati­tis (43%), in­fu­sion-re­lat­ed re­ac­tion (42%), fa­tigue (42%), ede­ma (40%), con­sti­pa­tion (40%), de­creased ap­petite (36%), nau­sea (36%), COVID-19 (24%), di­ar­rhea (21%), and vom­it­ing (21%). The most com­mon Grade 3 to 4 lab­o­ra­to­ry ab­nor­mal­i­ties (≥2%) were de­creased al­bu­min (7%), in­creased ala­nine amino­trans­ferase (4%), in­creased gam­ma‑glu­tamyl trans­ferase (4%), de­creased sodi­um (7%), de­creased potas­si­um (11%), de­creased mag­ne­sium (2%), and de­creas­es in white blood cells (17%), he­mo­glo­bin (11%), neu­trophils (36%), platelets (10%), and lym­pho­cytes (11%).

Se­ri­ous ad­verse re­ac­tions oc­curred in 37% of pa­tients who re­ceived RY­BRE­VANT^® in com­bi­na­tion with car­bo­platin and peme­trexed. Se­ri­ous ad­verse re­ac­tions in ≥2% of pa­tients in­clud­ed rash, pneu­mo­nia, ILD, pul­monary em­bolism, vom­it­ing and COVID-19. Fa­tal ad­verse re­ac­tions oc­curred in 7 pa­tients (4.6%) due to pneu­mo­nia, cere­brovas­cu­lar ac­ci­dent, car­dio-res­pi­ra­to­ry ar­rest, COVID-19, sep­sis, and death not oth­er­wise spec­i­fied.

RY­BRE­VANT^® as a Sin­gle Agent

For the 129 pa­tients in the CHRYSALIS clin­i­cal tri­al who re­ceived RY­BRE­VANT^® as a sin­gle agent, the most com­mon ad­verse re­ac­tions (≥20%) were rash (84%), IRR (64%), parony­chia (50%), mus­cu­loskele­tal pain (47%), dys­p­nea (37%), nau­sea (36%), fa­tigue (33%), ede­ma (27%), stom­ati­tis (26%), cough (25%), con­sti­pa­tion (23%), and vom­it­ing (22%). The most com­mon Grade 3 to 4 lab­o­ra­to­ry ab­nor­mal­i­ties (≥2%) were de­creased lym­pho­cytes (8%), de­creased al­bu­min (8%), de­creased phos­phate (8%), de­creased potas­si­um (6%), in­creased al­ka­line phos­phatase (4.8%), in­creased glu­cose (4%), in­creased gam­ma-glu­tamyl trans­ferase (4%), and de­creased sodi­um (4%).

Se­ri­ous ad­verse re­ac­tions oc­curred in 30% of pa­tients who re­ceived RY­BRE­VANT^®. Se­ri­ous ad­verse re­ac­tions in ≥2% of pa­tients in­clud­ed pul­monary em­bolism, pneu­moni­tis/ILD, dys­p­nea, mus­cu­loskele­tal pain, pneu­mo­nia, and mus­cu­lar weak­ness. Fa­tal ad­verse re­ac­tions oc­curred in 2 pa­tients (1.5%) due to pneu­mo­nia and 1 pa­tient (0.8%) due to sud­den death.

Please read full Pre­scrib­ing In­for­ma­tion for RY­BRE­VANT^®. 

cp-213274v4

 Ref­er­ences:

1. World Health Or­ga­ni­za­tion. Lung Can­cer. Ac­cessed Feb­ru­ary 2024. https://www.who.int/news-room/fact-sheets/de­tail/lung-can­cer

2. Amer­i­can Can­cer So­ci­ety. What is Lung Can­cer? Ac­cessed March 2024. https://www.can­cer.org/can­cer/types/lung-can­cer/about/what-is.html

3. Na­tion­al Li­brary of Med­i­cine. EGFR ex­on 20 in­ser­tion mu­ta­tions in non-small cell lung can­cer. Ac­cessed Feb­ru­ary 2024. https://www.ncbi.nlm.nih.gov/pmc/ar­ti­cles/PMC8799012/#:~:text=EGFR%20ex­on%2020%20in­ser­tions%20(EGFR,EGFR%20Ex20Ins%20have%20been%20dis­cov­ered

4. Amer­i­can Lung As­so­ci­a­tion. EGFR and Lung Can­cer. Ac­cessed Feb­ru­ary 2024.
https://www.lung.org/lung-health-dis­eases/lung-dis­ease-lookup/lung-can­cer/symp­toms-di­ag­no­sis/bio­mark­er-test­ing/egfr

5. Khad­dour K, et al. Can­cers (Basel). 2021;13(13):3164.

6. Riess JW, Gan­dara DR, Framp­ton GM, et al. Di­verse EGFR ex­on 20 in­ser­tions and co-oc­cur­ring mol­e­c­u­lar al­ter­ations iden­ti­fied by com­pre­hen­sive ge­nom­ic pro­fil­ing of NSCLC. J Tho­racic On­col. 2018;13(10):1560-1568.

7. Bazhen­o­va L, Min­chom A, Vi­teri S, et al. Com­par­a­tive clin­i­cal out­comes for pa­tients with ad­vanced NSCLC har­bor­ing EGFR ex­on 20 in­ser­tion mu­ta­tions and com­mon EGFR mu­ta­tions. Lung Can­cer. 2021;162:154-161.

8. RY­BRE­VANT® Pre­scrib­ing In­for­ma­tion. Hor­sham, PA: Janssen Biotech, Inc.

9. Na­gasa­ka M, Go­to K, Gomez J, et al. Ami­van­tam­ab in com­bi­na­tion with chemother­a­py in pa­tients with ad­vanced
non-small cell lung can­cer (NSCLC). Poster pre­sent­ed at IASLC World Con­fer­ence on Lung Can­cer. 8-14, 2021.

10. Ref­er­enced with per­mis­sion from the NC­CN Clin­i­cal Prac­tice Guide­lines in On­col­o­gy (NC­CN Guide­lines®) for Non-Small Cell Lung Can­cer V.4.2024. Ac­cessed March 2024. © Na­tion­al Com­pre­hen­sive Can­cer Net­work, Inc. 2024. All rights re­served. Ac­cessed April 1, 2024. To view the most re­cent and com­plete ver­sion of the guide­line, go on­line to NC­CN.org.

11. Vyse S, Huang PH. Tar­get­ing EGFR ex­on 20 in­ser­tion mu­ta­tions in non-small cell lung can­cer. Sig­nal Trans­duct Tar­get Ther. 2019;4:5. Pub­lished 2019 Mar 8. doi:10.1038/s41392-019-0038-9