664P - Impact of treatment beyond progression (TBP) in patients treated with immunotherapy (IO) in phase I trials (Ph1)

Background

The pseudoprogression has been described with the use of IO. Specific response criteria such as iRECIST, where pts continue TBP if clinically stable, have been developed. However, iRECIST is still not validated, and the true impact of this in Ph1 is still unclear.

Methods

We retrospectively reviewed the electronic health records of pts participating in IO Ph1 at Vall d'Hebron Hospital. Pts with TBP were selected. Clinicopathological and lab values were correlated with TBP outcomes based on RECIST V1.1 and iRECIST. Kaplan-Meier time-to-event analysis was performed. PFS-TBP was defined as the time from RECIST PD (iuPD) to (icPD).

Results

From August 2015 to March 2024, 884 pts received IO out of which 137 (16%) pts received TBP. 33% were female with a median age of 61 yrs (Q1-Q3 51-70). Main Tumor types were colorectal cancer (CRC) (n=25; 18%), melanoma (MM) (n=21; 15%), head & neck cancer (HN) (n=15; 11%), and other (n=76; 56%). Median PFS by RECIST V1.1 was 2.1 months (m) (95%CI 1.9-3.5). Median PFS-TBP was 1.4 m (95%CI 1.4-1.8) and the median duration of TBP was 1.2 m (95%CI 1-1.6). 1 pts achieved a complete response, 3 pts achieved a partial response, 12 pts stable disease, and 121 pts (%) achieved progressive disease as the best response after TBP. Among pts achieving PR or SD after RECIST PD, the median duration of disease of control was 2.2 m (95%CI 1.6-NA). No significant differences were observed in clinicopathological variables between pts achieving PD vs PR/SD after the first PD. TBP was well tolerated and only 19 % of new AEs were reported, mainly G1-G2 skin, endocrine, and digestive disorders.

Conclusions

Only a small proportion of pts meet the clinical criteria to continue treatment beyond PD. However, a subset of pts who continue TBP will benefit from this approach. Further prospective data will be required for better pts. selection for IO TBP.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.J. Lostes Bardaji: Non-Financial Interests, Personal, Research Funding: Digicore. O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Institutional, Writing Engagement: Roche, Merck; Other, Travel Expenses: Kyowa kirin, Almirall; Other, Travel Expenses and Conference Fee: Sanofi; Other, Travel expenses: Recordati. D. Morchón Araujo: Financial Interests, Personal, Invited Speaker: Astellas Pharma, PharmaMar. E. Muñoz-Couselo: Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Pierre Fabre, Sun Pharma, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, Sanofi, MSD, Pierre Fabre. M. Vieito: Financial Interests, Personal, Invited Speaker: Novocure; Financial Interests, Personal, Other, Steering committee member: BMS; Non-Financial Interests, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingelheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA Pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. A. Hernando Calvo: Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Institutional, Research Grant: Gilead; Other, Travel support: Merck Serono, Kyowa Kirin, Bristol Myers Squibb. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. All other authors have declared no conflicts of interest.