TEST:

Tempus HLA-LOH assay

β2M shRNA, beta–2–microglobulin short–hairpin RNA; CD, cluster of differentiation; EF1α, elongation factor–1 alpha; LIR, leukocyte immunoglobulin–like receptor; scFv, single–chain variable fragment; T2A, thosea asigna virus 2ADownload figure Open in new tab Download powerpoint Abstract 588 Figure 2 EVEREST-1 study design. BOIN, Bayesian optimal interval design; PCLD, preconditioning lymphodepletion; RP2D, recommended phase 2 dose

a May occur at any point in disease course. CRC, colorectal cancer; D, day; MESO, mesothelioma; NSCLC, non-small cell lung cancer; OVCA, ovarian cancer; PANC, pancreatic cancer; PCLD, preconditioning lymphodepletionDownload figure Open in new tab Download powerpoint Abstract 627 Figure 3 EVEREST-2 phase 1 dose escalation study design

This table includes patients enrolled in BASECAMP-1 with germline HLA-A*02 LOH status and correlative data available. Data as of 01 June 2024

P=Obs | N=200 | BASECAMP-1 (NCT04981119) | Sponsor: A2 Biotherapeutics Inc. | "Tempus AI...announced that the validation study of its human leukocyte antigen (HLA) loss of heterozygosity (LOH) investigational assay has been published in npj Precision Oncology...the study included analytical validation of an investigational test that detects HLA-LOH based on analysis of data generated from Tempus’ FDA-approved, next generation sequencing-based xT CDx assay...The study evaluated the test’s ability to accurately detect HLA-LOH in clinical samples with >=40% tumor cells. In collaboration with A2 Biotherapeutics, Tempus analyzed data from an observational clinical trial (NCT04981119), and demonstrated the feasibility of identifying HLA-LOH patients and accruing them into prospective studies by leveraging analysis of routinely obtained clinical diagnostic data. Results support the assay's use as an investigational device for precision oncology clinical trial use."

P | "Clinical Trial Registration Number: NCT04981119"

Mol Immunol. 2020.

Importantly, HLA-A/B/C alleles were almost always lost together, indicating that HLA loss most frequently occurs through haplotype loss, informing a strategy to direct multiplexed TCR-T to the remaining HLA haplotype. Conclusions Overall, these data highlight the importance of a multiplexed TCR-T cell therapy targeting various intact tumor antigens presented on intact HLA alleles in order to effectively address solid tumors.

The primary objective of phase 1 is to evaluate the safety and tolerability of A2B530 in patients with NSCLC, CRC, and PANC, and to identify the maximum tolerated dose and recommended phase 2 dose (RP2D). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B530.

BASECAMP-1 is an ongoing prescreening study to: 1) Identify patients with tumor-associated HLA LOH and eligible for Tmod CAR T-cell therapy, and 2) Obtain leukapheresis in preparation for the autologous CAR T-cell therapy trials EVEREST-1 (A2B530 targeting carcinoembryonic antigen; NCT05736731) and EVEREST-2 (A2B694 targeting mesothelin). We have identified 52 patients across sites with study-specific disease types with HLA-A*02:01 LOH; of these, 13 are currently being screened, 23 have been found ineligible, and 16 have consented. This demonstrated the feasibility of leveraging a diagnostic during routine clinical workup to identify rare, molecularly defined patients for personalized clinical studies.

"Tempus...announced that the U.S. Food & Drug Administration (FDA) has granted the company Breakthrough Device Designation for its HLA-LOH assay as a companion diagnostic (CDx) test. The test uses a machine learning model to analyze sequence data produced by Tempus’ FDA-approved, next generation sequencing-based xT CDx assay. It is intended to identify cancer patients with solid tumors who may benefit from treatment with specific targeted therapies when a patient’s tumor has experienced allele-specific loss of heterozygosity (LOH) for specific human leukocyte antigen (HLA) Class I alleles."