Immune Profile Score Could Enhance Immunotherapy Decision-Making in Solid Tumors

The immune profile score (IPS) algorithmic test may help clarify treatment decisions for certain subgroups of patients with solid tumors who are candidates for immunotherapy, according to Sandip P. Patel, MD, who added that future iterations of transcriptomic-based immune biomarkers may also address gaps in the immunotherapy armamentarium across disease sites.

“There are multiple reasonable standard-of-care [SOC] options in which an IPS score may drive a treatment decision [among those options],” Patel said in an interview with OncLive®.

Data from a retrospective validation study presented at the 2024 SITC Annual Meeting showed IPS to be a generalizable multi-omic biomarker that was prognostic for benefit from immune checkpoint inhibitor–based regimens among patients with solid tumors.¹ The study showed IPS to have significant prognostic utility for overall survival beyond tumor mutational burden (TMB; IPS-high/TMB-low to IPS-low/TMB-low HR, 0.49; 90% CI, 0.41-0.58), microsatellite instability (MSI; IPS-high/microsatellite stable [MSS] to IPS-low/MSS HR, 0.41; 90% CI, 0.32-0.53), and PD-L1 (IPS-high/PD-L1–negative to IPS-low/PD-L1–negative HR, 0.43; 90% CI, 0.33-0.56). Within the non–small cell lung cancer (NSCLC) cohort specifically (n = 647), IPS was prognostic for immune checkpoint inhibitor benefit beyond PD-L1 score (IPS-high/PD-L1–negative to IPS-low/PD-L1–negative HR, 0.43; 90% CI, 0.30-0.63).

These data supported the November 2024 release of the IPS algorithmic test for adult patients with stage IV and metastatic solid tumors who are already considered candidates for therapy with immune checkpoint inhibitors.²

In the interview, Patel, a professor of medicine in the Department of Medicine at the University of California San Diego, discussed the functionality of the IPS test, the current role of IPS as a biomarker in clinical practice, and where the future may be headed for immunotherapy drug development based on advances in biomarker-based patient classification.

OncLive: What is IPS, and how does it function as a biomarker in solid tumors?

Patel: IPS is a transcriptomic-based immune sensitivity classifier that’s part of the Tempus platform; a tumor undergoes sequencing and then is classified as IPS high vs IPS low, based on a retrospective analysis of patients who benefited from immune checkpoint blockade vs [those who did] not. [In the analysis, data showed] patients with IPS high–classified tumors had enhanced responses to immune checkpoint blockade, whereas patients with IPS-low tumors had less benefit with the use of immune checkpoint blockade agents in a real-world dataset. The data for IPS high vs low [in this analysis] were presented at the 2024 SITC Annual Meeting and demonstrated predictive utility [with IPS] above and beyond the known biomarkers of PD-L1, MSI status, and TMB.

How could the IPS test help oncologists guide treatment selection for patients with solid tumors?

The IPS test, which was derived across more than 16 cancer types, can help inform clinical scenarios in which immune checkpoint blockade by itself may be insufficient among the SOC treatment options a patient may have. For example, in thoracic oncology and NSCLC, for [patients with a] PD-L1 combined positive score greater than 50%, we do not yet know whether immunotherapy monotherapy—such as with PD-1–directed therapies—or chemotherapy/PD-1 inhibitor combinations are preferred. TMB and the patient’s ability to tolerate chemotherapy are 2 current factors that drive this decision-making.

IPS can help [identify] patients who are IPS high and may not benefit as much from chemotherapy, whereas patients who are transcriptomically more likely to be IPS low may benefit from the addition of chemotherapy [to immune checkpoint blockade in the treatment of] their PD-L1–high tumor.

How might the IPS test help propel future immunotherapy development?

IPS and other transcriptomic-based immune biomarkers [represent] one way in which we can better understand which patient populations can benefit from the existing immune checkpoint blockade agents, which target CTLA-4 and the PD-1/PD-L1 axis. However, equally importantly, [these biomarkers can help us learn more about the utility of] novel immune targets that are currently in clinical development. Next-generation versions of this test will help inform which patients could benefit from investigational therapeutic strategies, and similarly, [inform] how genomically guided biomarkers help improve drug development for targeted therapies. Future iterations of IPS may inform which patients may benefit from novel therapeutic strategies.

How do you plan to use this test in your clinical practice?

We’ve been working on developing the IPS test for a couple years, so I was eagerly awaiting its deployment in the SOC setting. [The IPS test] is now available, along with the Tempus xT and xR assays, which include the RNA sequencing component, by which one can have a report to classify a tumor as IPS high vs IPS low. [In NSCLC], this is most informative in the SOC setting, in which we have 2 reasonable treatment options involving immunotherapy, but we don’t yet know how best to select patients, for example, [to receive] chemoimmunotherapy vs immunotherapy alone in PD-L1–high NSCLC.

There are likely other clinical contexts in which immunotherapy alone may not be the optimal choice, such as, for example, in a patient who is IPS low. [Furthermore], a patient who may be IPS high may not necessarily need as much chemotherapy or may not need chemotherapy at all if their tumor is going to be sensitive to the immunologic component [of a regimen]. That is the area in which this test will most likely see utility, and I plan on considering it in my clinical practice.

References

1. Tempus announces the clinical launch of its Immune Profile Score algorithmic test. News release. Tempus AI. November 7, 2024. Accessed December 4, 2024. https://www.tempus.com/news/pr/tempus-announces-the-clinical-launch-of-its-immune-profile-score-algorithmic-test/
2. Zander AD, Erbe R, Liu Y, et al. Clinical validation of a novel multi-omic algorithm for stratifying outcomes in a real-world cohort of metastatic solid cancer patients treated with immune checkpoint inhibitors. J Immunother Cancer. Published online November 05, 2024. doi:10.1136/jitc-2024-SITC2024.0188