Merck Advances Oncology Portfolio and Pipeline

Mer­ck­ab­stracts today announced more than 30 abstracts will be pre­sent­ed at the Euro­pean Soci­ety for Med­ical Oncol­o­gy (ESMO) Vir­tu­al Con­gress 2020 from Sep­tem­ber 19–21. The abstracts span the Company’s clin­i­cal pro­gram in oncol­o­gy across sev­er­al inno­v­a­tive modal­i­ties and mech­a­nisms that have the poten­tial to advance treat­ment across a range of tumor types includ­ing bil­iary tract, lung and urothe­lial (blad­der) cancers.

“Our oncol­o­gy ambi­tion is to dis­cov­er inno­v­a­tive ther­a­pies with trans­for­ma­tive results. The data being pre­sent­ed in urothe­lial can­cer demon­strate this approach in action, where we are see­ing promis­ing results for a new first-line main­te­nance ther­a­peu­tic option with BAVENCIO^® in this form of can­cer,” said Luciano Ros­set­ti, Glob­al Head of Research & Devel­op­ment for the Bio­phar­ma busi­ness of Mer­ck. “In addi­tion, long-term fol­low up data in advanced lung can­cer from two of our in-house devel­oped mechanisms—our oral MET inhibitor, tepo­tinib, and our first-in-class bifunc­tion­al fusion pro­tein immunother­a­py tar­get­ing TGF‑β/PD-L1, bin­tra­fusp alfa—continue to show sus­tained impact in one of the lead­ing caus­es of can­cer mortality.”

(Pre­sen­ta­tions #699O; 704MO; 745P). Pri­ma­ry results from the JAVELIN Blad­der 100 study demon­strat­ed an over­all sur­vival (OS) ben­e­fit for BAVENCIO vs. best sup­port­ive care in the first-line main­te­nance treat­ment of advanced urothe­lial car­ci­no­ma, mak­ing BAVENCIO the first and only immunother­a­py to sig­nif­i­cant­ly pro­long OS in this set­ting. Three new abstracts from the JAVELIN Blad­der 100 study will be pre­sent­ed at ESMO:

• An oral pre­sen­ta­tion dur­ing the Prof­fered Paper 1 – GU, non-prostate ses­sion sched­uled on Sep­tem­ber 19, 2020 at 5:28pm–5:40pm CEST/11:28am-11:40am EDT, will high­light asso­ci­a­tions between clin­i­cal out­comes and explorato­ry bio­mark­ers (Pre­sen­ta­tion #699O)
• Two oth­er abstracts pro­vide more infor­ma­tion on pre­spec­i­fied sub­group analy­ses, as well as patient-report­ed outcomes.

(Pre­sen­ta­tion #910O). Pri­ma­ry results from this Phase III study will be pre­sent­ed. The study is a demon­stra­tion of our com­mit­ment to devel­op options for patients with squa­mous cell car­ci­no­ma of the head and neck, and the results increase under­stand­ing in the field of the role of immunotherapy.

(Pre­sen­ta­tions: #1283P; 1286P; 1347P). Three posters from the largest study in patients with non-small cell lung can­cer (NSCLC) har­bor­ing METex14 skip­ping treat­ed with tepotinib—an oral, once-dai­ly, high­ly selec­tive MET inhibitor. Data pre­sent­ed will highlight:

• Durable clin­i­cal activ­i­ty that has been con­sis­tent across clin­i­cal­ly rel­e­vant sub­groups both in treat­ment-naïve and in pre­vi­ous­ly treat­ed patients as well as in patients with brain metas­tases as assessed by liq­uid biop­sy or tis­sue biop­sy (Poster #1283P)
• Health-relat­ed qual­i­ty of life (HRQoL) has been shown to be main­tained, with clin­i­cal­ly mean­ing­ful delays in the time to dete­ri­o­ra­tion of cough, dys­p­nea, and chest pain (Poster #1286P)
• A safe­ty pro­file con­sist­ing of most­ly mild to mod­er­ate adverse events with few treat­ment discontinuations.

The INSIGHT 2 study assess­ing the com­bi­na­tion of osimer­tinib and tepo­tinib in patients with EGFR-mutant NSCLC that has devel­oped resis­tance to first-line osimer­tinib treat­ment due to MET ampli­fi­ca­tion is ongo­ing and active­ly recruit­ing patients (Poster #1415TiP).

Data from the INTR@PID clin­i­cal tri­al pro­gram for first in-class bin­tra­fusp alfa, an inves­ti­ga­tion­al bifunc­tion­al fusion pro­tein, tar­get­ing both TGF‑β and PD-L1 path­ways, shows promis­ing and durable respons­es across mul­ti­ple tumor types includ­ing NSCLC and bil­iary tract can­cer (BTC) with a man­age­able safe­ty pro­file in Phase I expan­sion cohorts.

Two long-term fol­low-up stud­ies assess­ing effi­ca­cy and safe­ty from the INTR@PID clin­i­cal tri­al pro­gram will be pre­sent­ed as posters at ESMO 2020:

In addi­tion, pre­lim­i­nary analy­sis will be pre­sent­ed in a mini-oral pre­sen­ta­tion (#616MO) from a tri­al con­duct­ed by the Nation­al Can­cer Insti­tute (NCI), the Quick Effi­ca­cy Seek­ing Tri­al (QuEST) inves­ti­gat­ing a triple com­bi­na­tion ther­a­py (BN-brachyury [BVax] + bin­tra­fusp alfa + N‑803) in cas­tra­tion-resis­tant prostate can­cer. Avail­able on demand from Sep­tem­ber 18 at www.ESMO.org.

For the Company’s first biol­o­gy-dri­ven leader ERBITUX, a num­ber of inves­ti­ga­tor-spon­sored stud­ies (ISS), includ­ing in com­bi­na­tion with BAVENCIO (avelum­ab), con­tin­ue to demon­strate its steady role across the con­tin­u­um of care in metasta­t­ic col­orec­tal can­cer, and back­bone of treat­ment of squa­mous cell car­ci­no­ma of the head and neck. Data demon­strat­ing the role of ERBITUX as a promis­ing com­bi­na­tion part­ner include an oral pre­sen­ta­tion inves­ti­gat­ing avelum­ab plus cetux­imab in pre-treat­ed RAS wild type metasta­t­ic col­orec­tal can­cer patients as rechal­lenge strat­e­gy: the Phase II CAVE (cetux­imab-avelum­ab) mCRC study. This will be pre­sent­ed dur­ing the Prof­fered Paper GI – col­orec­tal ses­sion sched­uled on Sep­tem­ber 19, 2:49pm‑3:01pm CEST/8:49am‑9:01am EDT (Pre­sen­ta­tion #397O)

*BAVENCIO is under clin­i­cal inves­ti­ga­tion for the first-line main­te­nance treat­ment of advanced UC and not yet approved in any mar­kets out­side of the US.

^†Tepo­tinib is the Inter­na­tion­al Non­pro­pri­etary Name (INN) for the MET kinase inhibitor MSC2156119J. Tepo­tinib is cur­rent­ly under clin­i­cal inves­ti­ga­tion in NSCLC and not yet approved in any mar­kets out­side of Japan.

^‡Bin­tra­fusp alfa is cur­rent­ly under clin­i­cal inves­ti­ga­tion and not approved for any use any­where in the world.

BAVENCIO is a human anti-pro­grammed death ligand‑1 (PD-L1) anti­body. BAVENCIO has been shown in pre­clin­i­cal mod­els to engage both the adap­tive and innate immune func­tions. By block­ing the inter­ac­tion of PD-L1 with PD‑1 recep­tors, BAVENCIO has been shown to release the sup­pres­sion of the T cell-medi­at­ed anti­tu­mor immune response in pre­clin­i­cal mod­els. In Novem­ber 2014, Mer­ck and Pfiz­er announced a strate­gic alliance to co-devel­op and co-com­mer­cial­ize BAVENCIO.

The Euro­pean Com­mis­sion has autho­rized the use of BAVENCIO in com­bi­na­tion with axi­tinib for the first-line treat­ment of adult patients with advanced renal cell car­ci­no­ma (RCC). In Sep­tem­ber 2017, the Euro­pean Com­mis­sion grant­ed con­di­tion­al mar­ket­ing autho­riza­tion for BAVENCIO as a monother­a­py for the treat­ment of adult patients with metasta­t­ic Merkel cell car­ci­no­ma (MCC).

In the US, BAVENCIO^® (avelum­ab) is indi­cat­ed for the main­te­nance treat­ment of patients with local­ly advanced or metasta­t­ic urothe­lial car­ci­no­ma (UC) that has not pro­gressed with first-line plat­inum-con­tain­ing chemother­a­py. BAVENCIO is also indi­cat­ed for the treat­ment of patients with local­ly advanced or metasta­t­ic urothe­lial car­ci­no­ma who have dis­ease pro­gres­sion dur­ing or fol­low­ing plat­inum-con­tain­ing chemother­a­py, or have dis­ease pro­gres­sion with­in 12 months of neoad­ju­vant or adju­vant treat­ment with plat­inum-con­tain­ing chemotherapy.

BAVENCIO in com­bi­na­tion with axi­tinib is indi­cat­ed in the US for the first-line treat­ment of patients with advanced renal cell car­ci­no­ma (RCC). Addi­tion­al­ly, the US Food and Drug Admin­is­tra­tion (FDA) grant­ed accel­er­at­ed approval for avelum­ab (BAVENCIO^®) for the treat­ment of adults and pedi­atric patients 12 years and old­er with metasta­t­ic Merkel cell car­ci­no­ma (MCC). This indi­ca­tion is approved under accel­er­at­ed approval based on tumor response rate and dura­tion of response. Con­tin­ued approval for this indi­ca­tion may be con­tin­gent upon ver­i­fi­ca­tion and descrip­tion of clin­i­cal ben­e­fit in con­fir­ma­to­ry trials.

BAVENCIO is cur­rent­ly approved for patients with MCC in 50 coun­tries glob­al­ly, with the major­i­ty of these approvals in a broad indi­ca­tion that is not lim­it­ed to a spe­cif­ic line of treatment.

The spe­cial warn­ings and pre­cau­tions for use for BAVENCIO monother­a­py include infu­sion-relat­ed reac­tions, as well as immune-relat­ed adverse reac­tions that include pneu­moni­tis and hepati­tis (includ­ing fatal cas­es), col­i­tis, pan­cre­ati­tis (includ­ing fatal cas­es), myocardi­tis (includ­ing fatal cas­es), endocrinopathies, nephri­tis and renal dys­func­tion, and oth­er immune-relat­ed adverse reac­tions. The spe­cial warn­ings and pre­cau­tions for use for BAVENCIO in com­bi­na­tion with axi­tinib include hepatotoxicity.

The SmPC list of the most com­mon adverse reac­tions with BAVENCIO monother­a­py in patients with sol­id tumors includes fatigue, nau­sea, diar­rhea, decreased appetite, con­sti­pa­tion, infu­sion-relat­ed reac­tions, weight decreased and vom­it­ing. The list of most com­mon adverse reac­tions with BAVENCIO in com­bi­na­tion with axi­tinib includes diar­rhea, hyper­ten­sion, fatigue, nau­sea, dys­pho­nia, decreased appetite, hypothy­roidism, cough, headache, dys­p­nea, and arthralgia.