273MO - DURANCE: A phase Ib/II study to assess the safety and activity of durvalumab (MEDI4736) in combination with S-488210/S-488211 vaccine in non-muscle invasive bladder cancer

Background

High-risk Non-Muscle Invasive Bladder Cancer (hrNMIBC) is characterised by a high recurrence rate despite endoscopic resection and adjuvant Bacillus Calmette-Guérin (BCG). Keynote-057 showed encouraging results for immunotherapy in BCG-unresponsive NMIBC. Peptide-based cancer vaccines may enhance efficacy of immunotherapy.

Methods

Patients with recurrent hrNMIBC after intravesical resection and optimal BCG treatment were included. Patients received a new intravesical resection followed by durvalumab 1500 mg every 4 weeks for up to 7 doses and concomitant subcutaneous injections of S-488210/S-488211 peptide vaccine weekly for 6 weeks and then biweekly for up to 16 doses. Primary endpoint of phase Ib was to assess safety and tolerability of the combination as per CTCAE criteria (v5.0). Initial treatment response was evaluated by cystoscopy at 12 weeks.

Results

Between March 2022 and April 2024, 14 patients received at least one dose of durvalumab and 3 doses of S-488210/S-488211 and were therefore evaluable for safety analysis. At least one adverse event (AE) was reported for 13/14 patients (92.9%) during the first 4 weeks of treatment (dose-limiting toxicities [DLT] period). Grade 1 (G1) injection site reaction due to vaccine administration was the most common treatment-related AE (50%), followed by G1 pruritus (14.3%) and G1 decrease in thyroid stimulating hormone levels (14.3%). Three serious AEs (haematuria, lung infection, and maculopapular rash) were observed in 1/14 patients (7.1%) during DLT period, all of which were considered unrelated to the trial treatment. No DLT, G3 treatment-related AEs, or G4-5 AEs were observed. As of June 2024, response data were available for 12/14 patient. No tumour lesions were identified via cystoscopy at 12 weeks in 8/12 (66.7%) patients, including 4/8 (50%) patients with pre-existing carcinoma in situ (CIS) who demonstrated a complete response.

Conclusions

Co-administration of durvalumab and S-488210/S-488211 vaccine is safe and well tolerated. The encouraging response rate at the first cystoscopy assessment warrants further investigation of this combination in the phase II trial.

Clinical trial identification

NCT04106115.

Editorial acknowledgement

Legal entity responsible for the study

University College London.

Funding

AstraZeneca and Shionogi Ltd.

Disclosure

B.E. Szabados: Financial Interests, Personal, Other, travel funding: Roche/Genentech, Photocure; Financial Interests, Personal, Invited Speaker: MSD, Pfizer; Financial Interests, Personal, Advisory Board: Ellipses, Merck kga, Ipsen. D. Enting: Financial Interests, Institutional, Invited Speaker, Janssen Prostate Cancer UK Summit: Janssen; Financial Interests, Institutional, Advisory Board, Ra223 ad board: Bayer; Financial Interests, Institutional, Other, Bladder Cancer Preceptorship: Astellas; Financial Interests, Institutional, Invited Speaker, Prostate Cancer Preceptorship speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Advisory Board: AstraZeneca. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers-Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Other, honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers-Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead. C.H.H. Ottensmeier: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Roche Genentech; Financial Interests, Personal, Other, consulting: Sebastian Bio; Financial Interests, Personal, Other, head of SAB: Neuvogen; Financial Interests, Personal, Stocks/Shares: Neuvogen; Financial Interests, Institutional, Research Grant, trial funding: Verastem, Merck Sharpe and Dohme; Financial Interests, Institutional, Coordinating PI, phase I trial: Transgene; Financial Interests, Institutional, Coordinating PI: Delcath Systems, PsiOxus, Touchlight genetics; Financial Interests, Personal, Coordinating PI, Coordinating PI on two clinical trials: BioNTech; Financial Interests, Institutional, Research Grant, trial funding to previous employer (HARE40 trial): BioNTech. S. Quezada: Financial Interests, Personal, Advisory Board: DROIA oncology; Financial Interests, Personal, Full or part-time Employment: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares: Achilles Therapeutics; Financial Interests, Personal, Royalties: Dartmouth College, MSKCC, UCL. M. Linch: Financial Interests, Personal, Advisory Board, 2 advisory boards over the past 12 months: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker, Guest speaker: Janssen, Bayer; Financial Interests, Personal, Other, IDMC consultant: Bicycle Therapeutics; Financial Interests, Personal, Advisory Board, One off advisory board: ADC Therapeutics; Financial Interests, Personal, Advisory Board, one off advisory board: AstraZeneca; Financial Interests, Institutional, Research Grant, Grant for investigator initiated trial: AstraZeneca, Shionogi Ltd, Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator, Co-ordinating investigator for MK-5684-003 trial: MSD; Non-Financial Interests, Personal, Principal Investigator, Co-ordinating investigator for ProMerit trial: BioNTech. All other authors have declared no conflicts of interest.