Phase I study of radiotherapy (RT) & durvalumab in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) & follicular lymphoma (FL): The RADD study.

Authors

null

Eliza Anne Hawkes

Austin Health and Olivia Newton-John Cancer Research Institute, Heidelberg, Australia

Eliza Anne Hawkes , Kate Manos , Geoffrey Chong , Jodie Palmer , Michael Patrick MacManus , Colm Keane , Andrew Mark Scott , Jake Shortt , David Ritchie , Leonid Churilov , Laura Johnston , Tom Witkowski , Allison Anne Barraclough , Sze Ting Lee , Wendi Lin , Rachel Koldej , Richard Khor

Organizations

Austin Health and Olivia Newton-John Cancer Research Institute, Heidelberg, Australia, Austin Health, Heidelberg, Australia, Olivia Newton-John Cancer Research Institute, Heidelberg, Australia, Peter MacCallum Cancer Inst, East Melbourne, VIC, Australia, Princess Alexandra Hospital, Woolloongabba, Australia, Monash University and Monash Health, Melbourne, Australia, Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne, Australia, University of Melbourne, Melbourne, Australia, Australian Cancer Research Foundation at Royal Melbourne Hospital, Melbourne, Australia

Research Funding

Other Foundation
Victorian Cancer Agency (grant funding - TRP16006), Pharmaceutical/Biotech Company

Background: Most DLBCL & FL responds well to first line treatment, yet relapsed disease outcomes are poor. PD1/PDL1 inhibitors yield high response rates in some lymphomas, but single agent therapy in heavily pre-treated pts are disappointing. RT stimulates anti-tumor immunity through several mechanisms and may enhance response to immune checkpoint inhibition (ICI). Concurrent ICI & RT is synergistic in preclinical studies & solid tumors, improving local & distant (abscopal) response. RT to multiple disease sites may broaden the spectrum of tumor antigen release and overcome clonal variation between disease sites to further augment the immune response. Methods: RaDD (NCT03610061) is a phase I, 3+3 dose escalation study to determine the safety profile of escalating dose & number of sites of RT in combination with Durvalumab (anti-PD-L1 antibody) in RR DLBCL & FL. Eligible pts (i.e. ≥1 prior therapy, ineligible for auto-SCT, no contraindication to PDL1i) receive 5 fractions of external beam RT to target site(s). 5 RT dose & site levels are included (dose range 2.5Gy-20Gy to 1-3 sites). Durvalumab 1500mg IV commences day 2 of RT and continues 4-weekly until confirmed disease progression. The DLT period is 28 days from start of RT. Primary endpoint is the recommended phase two dose (RP2D) of RT in combination with durvalumab. Secondary endpoints include response rates, PFS & OS. Correlative studies will examine the tumour-immune system interaction; an exploratory PET substudy with novel tracers for durvalumab (89Zr-Durvalumab) & CD8+ T cells (89Zr -Df-IAB22M2C) will also be performed. Projected enrollment for determination of maximum tolerated dose (MTD) & RP2D is 6-30 pts pending toxicity. Recruitment will continue to 36 pts for secondary endpoint analysis. 9 pts are enrolled across cohorts 1-3 to date. Clinical trial information: NCT03610061.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies

Sub Track

Non-Hodgkin Lymphoma

Clinical Trial Registration Number

NCT03610061

Citation

J Clin Oncol 38: 2020 (suppl; abstr TPS8075)

DOI

10.1200/JCO.2020.38.15_suppl.TPS8075

Abstract #

TPS8075

Poster Bd #

408

Abstract Disclosures