LBA7 - The Rome trial from histology to target: The road to personalize targeted therapy and immunotherapy

Background

The ROME Trial (NCT04591431) is a randomized multi-basket phase II trial evaluating the feasibility, efficacy, and safety of Targeted Therapy (TT) versus standard of care (SoC) in patients (pts) with solid tumors bearing actionable alterations identified by comprehensive genome profiling (CGP) and discussed by Molecular Tumor Board (MTB).

Methods

Tissue and blood samples of pre-treated (with at maximum two lines) pts, collected within 6 months (mos) before enrollment, underwent CGP with FoundationOne CDx and LiquidCDx. Following MTB discussion, pts bearing at least one targetable alteration were randomized 1:1 to TT at MTB choice or SoC at investigator choice. Crossover after progression or unacceptable toxicity was allowed. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results

1794 pts were screened across 40 Italian Centers, and 400 (22.5%) were randomized (TT/SoC = 200/200). The median age was 61 years (22-85). 38 different histologies were enrolled, including colorectal (16%), breast (10%), gastric (9%), glioblastoma (9%), and biliary tract cancers (9%). The most common targetable genomic alterations were hTMB (34%), PIK3CA/AKT/PTEN (19%), ERBB2 (14%), FGFR (8%) and MSI (4%). The most frequently assigned TTs were IPI/NIVO (37%), ipatasertib (16%), pemigatinib (8%), TDM1 (8%), and atezo/ipatasertib (6%).

ORR was 17.0% in the TT arm compared to 9.5% in the SoC arm (p = 0.026). The median PFS was 3.7 mos in the TT compared to 2.8 mos in the SoC arm (HR 0.64, 95% CI 0.51-0.80, p < 0.001). The 12-month PFS rate was 22% for TT and 7% for SoC. Median OS was 9.2 mo for TT vs. 7.6 mo for SoC (HR 0.89, 95% CI 0.68-1.13 p = 0.299).

As an exploratory analysis, pts with hTMB/MSS tumors receiving TT (immunotherapy) had a median PFS of 3.6 mo and a 12-month PFS rate of 32.7% compared to 2.8 mo and 6.3% in the SoC group (HR 0.65, 95% CI 0.42-0.92, p = 0.01). The incidence of G≥3 AEs was 35% for TT and 40% for SoC.

Conclusions

The ROME Trial demonstrated that a mutational-based treatment approach based on the MTB discussion of CGP results may significantly improve ORR and PFS compared to SoC in pretreated patients with metastatic solid tumors, particularly with immunotherapy.

Clinical trial identification

NCT04591431.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione per la Medicina Personalizzata (FMP).

Funding

Roche; Novartis; Pfizer; Bristol-Mayers-Squibb; Takeda Pharmaceutical Co.; Incyte; Merck; Eli Lilly.

Disclosure

A. Botticelli: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Lilly, Novartis, Daiichi Sankyo, Gilead; Financial Interests, Personal, Advisory Board: Pfizer, Seagen, AstraZeneca, MSD, Pierre Fabre; Financial Interests, Institutional, Coordinating PI: Gilead. S. Scagnoli: Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly; Financial Interests, Personal, Speaker’s Bureau: Pfizer, MSD, BMS, Pierre Fabre, Daiichi Sankyo, AstraZeneca, Amgen; Financial Interests, Institutional, Speaker, Consultant, Advisor: Gilead. P. Conte: Financial Interests, Personal, Advisory Board: Roche, Pfizer, MSD, Novartis, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, Exact Sciences. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck; Financial Interests, Institutional, Local PI: Seagen, Hutchinson. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, 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: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, Ose, Galecto and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, Ose, and MSD. M. Aglietta: Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Lilly, Pfizer, MSD, Novartis, Amgen, BMS. F. Mazzuca: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Novartis; Financial Interests, Personal, Advisory Board: Lilly, Pfizer, MSD, Amgen, BMS. E. Capoluongo: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche; Financial Interests, Personal, Advisory Board: Pfizer. 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, Diatech; Non-Financial Interests, Leadership Role, Scientific Secretary and Editor in Chief of The Journal of Liquid Biopsy (Oficial Journal of the Society): ISLB. M. Nuti: Financial Interests, Personal and Institutional, Research Funding: Incyte; Financial Interests, Personal, Advisory Board: Incyte. G. D'Amati: Financial Interests, Personal, Advisory Board: BMS, MSD. B. Cerbelli: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Roche, Novartis, AstraZeneca. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Invited Speaker: Illumina; Financial Interests, Institutional, Research Grant: Roche. G. Giannini: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca. F. Cognetti: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Lilly, Pfizer, Novartis, MSD, Amgen, BMS, Exact Science. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; 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, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient Advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Editor of Chief of ESMO Open: ESMO; Non-Financial Interests, Leadership Role, Until the end of 2024: EUSOMA. P. Marchetti: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Incyte, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: Celgene, Eisai, Merck; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Roche, Bristol Myers Squibb, Gentech; Financial Interests, Personal, Advisory Board: Amgen, Merck Serono; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Incyte, Roche, Lilly, Merck, Novartis, NanoString Technologies, Pierre Fabre, Pfizer, Takeda. All other authors have declared no conflicts of interest.