70MO - Genomic profiling to expand precision cancer medicine in the real world: The ROME trial

Background

The Rome Trial is a randomized phase II trial (NCT04591431) that aims to evaluate the efficacy of Extensive genomic profiling (EGP) guided Tailored Therapy (TT) in patients (pts) with metastatic solid tumors. Here we report the results of the first two years of EGP and its impact on Molecular Tumor Board (MTB) discussions.

Methods

Tissue (collected <6 months) and blood samples were analyzed with a centralized NGS assay. Four strata were defined: breast, GI non-colorectal, lung, and other cancers. EGP results were discussed by the MTB and pts bearing mutations deemed actionable by at least one of the drugs available for TT were randomized 1:1 to receive the selected TT or standard. When no genetic alteration actionable according to the drugs available was detected, the case was classified as Screening failure (SF).

Results

1319 pts were enrolled. EGP was obtained on tissue and liquid in 1121 pts (85%). 3.0% and 12.0% had only tissue or liquid biopsy available. The most commonly mutated genes were: TP53 53%, KRAS 22%, CDKN2A/B 20%, APC 17%, PIK3CA 17% PTEN 13%, ERBB2 11%, NRAS 10%, MTAP 10%. The 5 most frequent genes by strata were: breast cancer: TP53 60%, PIK3CA 49%, ESR1 28%, FGF/FGRF1 25%; Gi non-colorectal cancer: TP53 60%, KRAS 47%, CDKN2A/B 28%, APC 27%, PIK3CA 22%; lung cancer: TP53 60%, EGFR 28%, KRAS 26%, ERBB2 24%, CDKN2A/B 23%; other cancers: TP53 63%, KRAS 30%, APC 24%, CDKN2A/B 24%, PTEN 20%, TERT 18%. MSI status was found in 4% of pts, while 76% had MSS <10 mut/mb and 20% had MSS >10 mut/mb. 721 cases with relevant alterations were discussed in 101 weekly MTB meetings. 316 pts were randomized (24% enrolling rate). 167 SF pts still received a useful indication from MTB: 58 pts referred to another trial, 28 had a modification of the standard, and 81 pts were addressed to genetic counseling indicated by potential germline alterations. Collectively, 483/1319 (34%) screened pts received an indication based on EGP and MTB discussion.

Conclusions

The extensive NGS analysis performed in the ROME trial evidenced pathways commonly mutated in different cancer histologies and indicated actionable genetic alterations in a relevant number of patients. By providing also additional indications or treatment propositions, EGP and MTB discussion proved useful for about 34% of patients.

Clinical trial identification

NCT04591431.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Roche, Takeda, Lilly, BMS, Pfizer.

Disclosure

A. Botticelli: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, MSD, Novartis, Seagen; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, Novartis, MSD, Seagen. S. Scagnoli: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Lilly, Pfizer, MSD; Financial Interests, Personal, Advisory Board: Lilly. P.F. Conte: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, MSD, Novartis, Seagen; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, Novartis, MSD, Seagen, Exact Sciences. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Pierre Fabre, Nordic Pharma; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant and Advisory Role, Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: iTeos; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role, Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Personal, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Personal, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Personal, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Personal, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Personal, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. M. Aglietta: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, MSD, Novartis, Amgen, BMS; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, Novartis, MSD, Amgen, BMS. F. Mazzuca: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, MSD, Novartis, Amgen, BMS, BMS; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, MSD, Amgen; Financial Interests, Personal, Speaker’s Bureau: Novartis. E. Capoluongo: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. U. Malapelle: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, GSK, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis, Hedera. G. D'Amati: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: BMS, MSD. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Research Grant: Roche. G. Giannini: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD. F. Cognetti: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, MSD, Novartis, Amgen, BMS; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, Novartis, MSD, Amgen, BMS, Exact Sciences. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA. P. Marchetti: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Pfizer, Novartis, MSD, BMS; Financial Interests, Personal, Advisory Board: Roche, Lilly, Pfizer, MSD, Novartis, Seagen, Amgen, BMS, Exact Sciences. All other authors have declared no conflicts of interest.