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Regular and Young Investigator Award Abstracts
Clinical Trials In Progress
523 Preliminary clinical experience with XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors
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  1. Elaine Shum1,
  2. Matthew Reilley2,
  3. Yana Najjar3,
  4. Adil Daud4,
  5. John Thompson5,
  6. Joaquina Baranda6,
  7. R Donald Harvey7,
  8. Anthony Shields8,
  9. Ezra Cohen9,
  10. Shubham Pant10,
  11. Rom Leidner11,
  12. Alain Mita12,
  13. Roger Cohen13,
  14. Bartosz Chmielowski14,
  15. Mark Stein15,
  16. Siwen Hu-Lieskovan16,
  17. Catherine Fleener17,
  18. Ying Ding17,
  19. Lei Bao17,
  20. Sowmya Chollate17,
  21. Jolene Shorr17,
  22. Raphael Clynes17 and
  23. Barbara Hickingbottom17
  1. 1New York University, New York, NY, USA
  2. 2University of Virginia, Charlottesville, VA, USA
  3. 3University of Pittsburgh, Pittsburgh, PA, USA
  4. 4University of California, San Francisco, San Francisco, CA, USA
  5. 5University of Washington, Seattle, WA, USA
  6. 6University of Kansas Cancer Center, Kansas City, KS, USA
  7. 7Emory University School of Medicine, Atlanta, GA, USA
  8. 8Karmanos Cancer Center, Detroit, MI, USA
  9. 9University of California San Diego, La Jolla, CA, USA
  10. 10MD Anderson Cancer Center, Houston, TX, USA
  11. 11Providence Cancer Institute, Portland, OR, USA
  12. 12Cedars-Sinai Medical Center, Los Angeles, CA, USA
  13. 13Perelman School of Medicine at UPenn, Philadelphia, PA, USA
  14. 14UCLA, Los Angeles, CA, USA
  15. 15Columbia University, New York City, NY, USA
  16. 16Huntsman Cancer Institute, Salt Lake City, UT, USA
  17. 17Xencor, Inc., San Diego, CA, USA

Abstract

Background XmAb20717 is a humanized bispecific monoclonal antibody that simultaneously targets PD-1 and CTLA-4. We report updated data on patients treated at the recommended expansion dose from an ongoing, multicenter, Phase 1, dose-escalation and -expansion study of intravenous XmAb20717 in patients with selected advanced solid tumors that progressed after treatment with all standard therapies or with no standard therapeutic options.

Methods A maximum tolerated dose was not reached in dose escalation. XmAb20717 10 mg/kg every 2 weeks (Q2W) was selected as the expansion dose, based on consistent T-cell proliferation in peripheral blood indicative of dual PD-1/CTLA-4 checkpoint blockade, and response to treatment (RECIST[1.1]).1 Parallel expansion cohorts included ~20 patients each with melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and a basket of tumor types without an FDA-approved checkpoint inhibitor (CI). Patients treated with 10 mg/kg in dose escalation were pooled with expansion cohorts for analysis of clinical activity and safety.

Results As of 9 June 2021, 110 patients, ranging in age from 39 to 89 years and 66.4% male, were treated, and 5 were continuing treatment. Patients had received a median of 4 prior systemic treatment regimens, including CI therapy for 64.5%. The objective response rate was 13.0% (10/77 patients evaluable for efficacy), including 1 complete response (melanoma [confirmed]) and 9 partial responses (confirmed: 1 melanoma, 2 RCC, 2 CRPC, 1 ovarian cancer; unconfirmed: 1 melanoma, 2 NSCLC). The CRPC responders (2/7 with RECIST-measurable disease) had confirmed PSA decreases ≥ 50% from baseline (to 0.02 and 0.3 ng/mL); neither had progression on bone scans. All responders had prior CI exposure, except those with CRPC. Robust CD4 and CD8 T-cell activation was seen. Low baseline tumoral expression of myeloid recruitment genes, including IL-8, was associated with clinical benefit. Grade ≥ 3 immunotherapy-related adverse events in ≥ 3 patients included rash (16.4%), transaminase elevations (9.1%), hyperglycemia (4.5%), acute kidney injury (3.6%), amylase and lipase increased (2.7%), and lipase increased (2.7%).

Conclusions Preliminary data indicate 10 mg/kg XmAb20717 Q2W was associated with complete and partial responses in multiple tumor types and was generally well-tolerated in these heavily pretreated patients with advanced cancer. Changes in T-cell populations in the periphery and tumor are consistent with robust dual checkpoint blockade. These findings support further development of XmAb20717 in advanced solid tumors, including metastatic prostate cancer.

Trial Registration NCT03517488

References

  1. Shum E, Daud A, Reilley M, et al. Preliminary safety, pharmacokinetics/pharmacodynamics, and antitumor activity of XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors. JITC 2020;8(3):A247-8.

Ethics Approval The study was approved by each institution’s IRB.

https://doi.org/10.1136/jitc-2021-SITC2021.523

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