599P - R-IMMUNE: A phase Ib/II study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with locally advanced rectal cancer (LARC)

Background

There is a strong rationale to combine radiotherapy with immune checkpoint inhibitors (ICIs). This study evaluates this combination before surgery in locally advanced rectal cancer (LARC).

Methods

R-IMMUNE, a multicentric phase Ib/II trial, included patients with stage II/III LARC treated with a preoperative combination of radio-chemotherapy (45-50 Gy/25 fractions, 5FU 225 mg/m2/d, 5d/w from week 1 to 5) + atezolizumab 1200 mg/infusion (ATZ). The phase Ib evaluated a single infusion of ATZ at week 3. Phase II evaluated 4 infusions of ATZ at weeks 3, 6, 9 and 12. Surgery was planned for week 15. Safety and efficacy based on the pathological complete response (pCR) rate are primary objectives. Based on a two-stage Simon design, 33 patients (+3 for the replacement of non-evaluable patients) were required in phase II to detect an increase in pCR rate from 15% to 35% (α = 0.1, β = 0.1), with at least 8 pCRs to reject the null hypothesis.

Results

Six patients were included in phase Ib and 34 in phase II. This analysis covered 39 patients (median age 63 years, 56% male, 82% stage III, 12% MSI-H), excluding 1 phase II patient who is still undergoing treatment. A total of 193 adverse events (AEs) were reported, of which 29 (15%) were grade 3-4 and involved 19/39 (49%) of patients. Among gade 3-4 AEs, most frequent were urinary tract infections (6/29), blood disorders (5/29), post-operative anastomotic leaks/infections (4/29) and gastrointestinal disorders (4/29). Five patients presented immune-related AEs: 1 immune thrombocytopenia (grade 4), 2 endocrine disorders (grade 2) and 2 skin disorders (grade 1). So far, efficacy was assessed in 6 phase Ib patients and in 31 patients from the phase II (2 were excluded for protocol deviation). Respectively, 2/6 and 8/31 patients had a pCR. Overall, 10/37 (27%) patients had a pCR (including 2 MSI-H).

Conclusions

An analysis of the nearly complete R-immune cohort confirmed an acceptable safety profile and met study efficacy objectives. The results warrant further investigations of ICIs combined with radiotherapy in LARC eventually within a total neoadjuvant treatment and organ preservation based strategies.

Clinical trial identification

NCT03127007.

Editorial acknowledgement

Legal entity responsible for the study

Grand Hôpital de Charleroi – Belgium.

Funding

Roche.

Disclosure

J. Carrasco: Non-Financial Interests, Institutional, Research Funding: Roche, AstraZeneca; Financial Interests, Personal, Advisory Role: Seqalis. D. Schroeder: Financial Interests, Institutional, Invited Speaker, 1 presentation on 17/3/2023: AstraZeneca; Financial Interests, Personal, Other, Medical consultant: Institut de Pathologie et de Génétique Gosselies; Financial Interests, Institutional, Research Grant, Research grant paid to the laboratory in which I worked from Dec 2020 to Sep 2022: AbbVie; Other, Travel and congress grant for ESMO Sarcoma congress March 2023: PharmaMar. F. Sclafani: Financial Interests, Personal, Advisory Role: AMAL Therapeutics; Financial Interests, Personal, Advisory Board: Bayer, Bristol Myers Squibb, Dragonfly, Merck, Nordic Pharma, Roche, Servier; Financial Interests, Institutional, Research Funding: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Roche, Sanofi; Financial Interests, Personal, Funding, Travel grant: Amgen, Bayer, Lilly, Servier; Non-Financial Interests, Personal, Affiliate: EORTC. All other authors have declared no conflicts of interest.