158P - Patterns of immune-related adverse events in early-phase cancer immunotherapy trials

Background

The delivery of cancer immunotherapy often encounters complications from immune-related adverse events (irAEs). Analyzing irAEs in large clinical trials of checkpoint inhibitors (CPIs) has improved their management and surveillance. However, for non-standard cancer immunotherapies (CITs), aggregated clinical data on irAEs are scarce, and systematic exploration of these toxicities is lacking.

Methods

To systematically evaluate the pattern of irAEs across CITs and to examine the variability linked to concurrent CPI use and tumor burden metrics, we established a harmonized data mart from 23 early-phase trials, encompassing 12 molecules with diverse mechanisms targeting various cancers and involving a total of 3,568 patients.

Results

Our preliminary results reveal substantial variation in the incidence proportions of irAEs over a 3-month period across different CIT classes. Hepatitis (IQR: 17.7-34.2%), rash (IQR: 9.8-38.9%), and hypothyroidism (IQR: 0.3-2.5%) are the most common irAEs. Notably, a significant proportion of hepatitis cases are severe (grades 3-5, 44.4%), while rash and hypothyroidism are predominantly mild (grades 1-2, 92.7% and 97.2% respectively). Hepatitis is more frequent with systemic immunocytokines (50.4%) and related immune stimulators (35.1%), while targeted treatments with T-cell bispecifics (TCBs) are linked to organ-specific toxicities like rash (61.4%) and colitis (4.4%). The time-to-onset for severe irAEs, as indicated by the 10th percentile, also varied across CIT classes: TCBs and immunocytokines show effects within 1-3 days; immune modulators at 3-6 weeks; and treatments targeting the PD1/PD-L1 axis typically within 3-6 months. Finally, our analysis suggests that patients with liver metastases have a higher risk of developing hepatitis (hazard ratio [HR] = 2.0), but a lower risk of rash (HR = 0.8), a pattern also observed in patients with smaller target lesions (HR = 0.8).

Conclusions

In conclusion, our study provides insights into the occurrence of irAEs linked to non-standard CITs. More research is needed to uncover the molecular basis of these toxicities and help refine patient management and risk-benefit evaluations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

F. Hoffmann-La Roche AG.

Funding

F. Hoffmann-La Roche AG.

Disclosure

B.P. Fairfax: Financial Interests, Institutional, Advisory Board, I sit on a scientific advisory board for Roche regarding immunotherapy toxicity: Roche; Financial Interests, Institutional, Advisory Board, I have sat on a scientific advisory board for Pathios Therapeutics: Pathios Therapeutics; Financial Interests, Institutional, Invited Speaker, I have given a talk and provided consultancy for Immunocore and may provide further input for their work as a scientific advisor: Immunocore; Financial Interests, Personal, Advisory Board, I have given a talk and provided consultancy for UCB, last in 2022.: UCB; Financial Interests, Personal, Invited Speaker, I have provided an educational talk for Bristol Myers Squibb for local Oncology meeting in Birmingham UK and may provide further such talks.: BMS; Financial Interests, Personal, Invited Speaker, I have been asked to present my group's work at GSK in 2024: GSK; Financial Interests, Personal, Advisory Board, I have been asked to sit on a scientific advisory board for TCypher BIO: TCypher BIO. V.C. Schmid: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Achilles therapeutics. D.F. Lamparter: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche AG; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG, Verge Analytics, Lonza AG. T. Kam-Thong: Financial Interests, Personal, Full or part-time Employment: Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: Hoffmann-La Roche. P. Scepanovic, R. Mohindra: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. G. Duchateau-Nguyen: Financial Interests, Institutional, Full or part-time Employment: Hoffmann-La Roche; Financial Interests, Institutional, Stocks/Shares: Hoffmann-La Roche. A. Roller: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. V. Karanikas: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. D. Heinzmann, S.L. Mycroft: Financial Interests, Institutional, Full or part-time Employment: Roche; Financial Interests, Institutional, Stocks/Shares: Roche. C. Adams: Financial Interests, Personal, Full or part-time Employment, I am a scientist at Genentech.: Genentech; Financial Interests, Personal, Stocks/Shares, I have received RSUs/SARs as part of my compensation from Genentech.: Genentech. N. Städler: Financial Interests, Personal, Full or part-time Employment, employee of Roche: F. Hoffmann-La Roche AG; Financial Interests, Personal, Stocks/Shares, Roche Holding AG Genussscheine: F. Hoffmann-La Roche AG; Non-Financial Interests, Project Lead, As employee I lead projects: F. Hoffmann-La Roche AG.