Vanderbilt Symposium Highlights Recent Data on Novel Agents Under Evaluation in Hematologic Malignancies

Novel agents under evaluation in the field of hematologic oncology continue to break ground and Katie S. Gatwood, PharmD, BCOP, noted that cellular therapies such as obecabtagene autoleucel (obe-cel) and agents for the treatment of graft-vs-host disease (GVHD) including axatilimab (SNDX-6352) are among those to keep a close eye on.

Agents such as obe-cel, which the FDA accepted a biologics license application (BLA) for in January 2024 for the treatment of adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia, were among those discussed at the 2024 Vanderbilt Stem Cell Transplant and Cellular Therapy Symposium by Gatwood and collegues.¹ Obe-cel elicited a complete response (CR) rate of 54.3% with an incomplete count recovery (CRi) rate of 21.3% in infused patients (n = 94), according to data from the phase 2 FELIX study (NCT04404660).² Updated data from a pooled analysis of the study revealed that the CR/CRi rate was 78% (95% CI, 70%-85%) in the overall population (n = 127).³

“Awareness that these products are available [is key]”, Gatwood said. “Some of these [new or novel agents] such as the Orca products are available at certain community centers, but some may not be as accessible to patients at community oncology practices. Being able to increase awareness so that [providers] know that these options are available and to refer patients to a center that does have these clinical trial options open for patients is important.”

Additionally, the investigational monoclonal antibody targeting CSF-R1 axatilimab is among products Gatwood highlighted as having the potential to change practice; the FDA accepted the BLA for priority review of the agent for the treatment of patients with GVHD who received at least 2 prior lines of systemic therapy. The Prescription Drug User Fee Act date for the FDA decision is August 28, 2024. Data from the pivotal phase 2 AGAVE-201 study (NCT04710576) revealed that patients treated with 0.3 mg/kg of the agent every 2 weeks achieved an overall response rate of 74% (95% CI, 63%-83%) within the first 6 months of treatment.^4,5

In an interview with OncLive®, Gatwood, a clinical pharmacist specialist in Adult Stem Cell Transplant and Cellular Therapy at Vanderbilt University Medical Center in Nashville, Tennessee, discussed agents that she presented on at the symposium and future directions for novel therapeutics.

OncLive: What agents under evaluation have the potential to change practice?

Gatwood: Some of the [agents] that could change practice in the future include obe-cel which is a new CD19-[directed] autologous T-cell product which hopefully could result in better toxicity rates as well as improved outcomes [for patients]. That could be exciting to add into the cellular therapy space for some of our patients. New and emerging therapies [such as axatilimab] for treating GVHD [could] alter how we manage patients [and] offers another opportunity for treatment options to be used when we have [agents] that [patients do not respond to] particularly in the chronic GVHD space. The AGAVE-201 trial [evaluated] axatilimab in that space. A lot of [agents] of that nature where we have new cutting-edge data [have potential] to change practice in the very near future.

Are there certain institutional processes that have streamlined the delivery of standard or novel therapeutics?

Cellular therapy is a good example where we’ve gotten a good system down for how we onboard these products. Now as new therapies start to enter the market, we already have a structured approach of how we implement these therapies and [we are] engaging with the manufacturers to make sure that the onboarding process is as smooth and efficient as possible. We have a lot of set policies and procedures that we’re able to adjust to a new therapy, which makes it easier to implement in practice and get to patients sooner.

What are some of the gaps in data that future research could fill?

Gaps that exist [surround] continuing to [reduce the] toxicity of cellular therapies. One of the therapies that was mentioned during both the 2023 ASH Annual Meeting & Exposition and the 50th Annual Meeting of the EBMT was itacitinib and [investigators examined its] use for the management and prevention of cytokine release syndrome with cellular therapies. That’s an exciting [agent] that’s trying to address an unmet need that we have right now in treating patients who are receiving cellular therapies.

Also, the engineered grafts that are coming out—the Orca products in particular—are able to address a big unmet need and potentially offer a product that will provide patients with better outcomes [regarding] relapse as well as reducing GVHD even in comparison with some of our gold standard agents such as post-transplantation cyclophosphamide. Further research into these areas and continuing to see how these products do in further clinical trials, [including] more phase 3 clinical trials, will be important in seeing how they’re able to progress.

At Vanderbilt, we are involved in some of the Orca Bio trials looking at these engineered grafts. We’re actively enrolling patients on those trials now and we’re excited about [those trials] and trying to use [them] whenever we possibly can.

References

1. Autolus Therapeutics announces acceptance of biologics license application for obecabtagene autoleucel (obe-cel) as a potential treatment for relapsed/refractory adult B-cell acute lymphoblastic leukemia (ALL). News Release. Autolus Therapeutics. January 22, 2024. Accessed May 21, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-acceptance-biologics-license
2. Roddie C, Sandhu KS, Tholouli E, et al. Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): top line results of the pivotal FELIX study. J Clin Oncol. 2023;41(suppl 16):7000. doi:10.1200/JCO.2023.41.16_suppl.7000
3. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtagene autoleucel (obe-cel, AUTO1) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): pooled analysis of the ongoing FELIX phase Ib/II study. Blood. 2023;142(suppl 1):222. doi:10.1182/blood-2023-179454
4. Incyte announces U.S. Food and Drug Administration grants priority review for axatilimab for the treatment of chronic graft-versus-host disease. News release. Incyte. February 27, 2024. Accessed May 21, 2024. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-us-food-and-drug-administration-grants-priority
5. Incyte and Syndax present additional data from positive AGAVE-201 trial at ASH plenary session showing axatilimab efficacy including durable responses in chronic graft-versus-host disease. News release. Incyte. December 10, 2023. Accessed May 21, 2024. https://investor.incyte.com/news-releases/news-release-details/incyte-and-syndax-present-additional-data-positive-agave-201