BCMA/CD19 Dual-Targeting CAR-T GC012F Continues to Display Durable Response for RRMM in Updated Results
Data were presented at ASCO 2021 and EHA 2021 for the initial 19 patients. Now, investigators are painting a fuller picture with an additional 9.
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Investigators at the 2022 American Society of Clinical Oncology (ASCO) annual meetingare sharing outcomes for 9 additional patients in updated results from a first-in-human study (NCT04236011; NCT04182581) of GC012F, a B cell maturation antigen (BCMA)/CD19 dual-targeting CAR-T for patients with relapsed/refractory multiple myeloma (RRMM).1
Developed on the novel FasT CAR-T platform by Gracell, GC012F continued to produce deep and durable responses in patients with RRMM across 3 different dose levels while maintaining a favorable safety profile, according to investigators. The BCMA-CD19 dual FasT CAR-T is also able to be manufactured overnight, a differentiating factor compared with other cell therapies.
The single-arm, open label, multicenter, investigator-initiated trial enrolled heavily pretreated patients with RRMM (age range, 27–76) between October 2019 and November 2021. Data were presented at ASCO 2021 and EHA 2021 for the initial 19 patients. Now, investigators are reporting on the additional 9 (total n = 28).
Participants had tried a median of 5 prior lines of therapy (range, 2–9), and 24 of 28 patients were refractory to their last line of therapy. Additionally, 89.3% (25/28) were high risk (HR- mSMART), 8 patients had [extramedullary] disease, 1 patient presented with plasma cell leukemia, 3 never achieved complete response (CR) even after transplant, and 3 were primary refractory.
Prior lines of therapy included prior anti-CD38 for 9/28 patients and prior immunomodulatory drugs (IMiDs) for 27/28 patients. Nearly all (26/28) patients were refractory to proteasome inhibitors (PI) and IMiDs.
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Participants underwent lymphodepletion over 2-3 days with a regimen comprising 30 mg/m2/day fludarabine + 300 mg/m2/day cyclophosphamide before receiving a single infusion of GC012F at doses of 1x105/kg (DL1) (n = 2), 2x105/kg (DL2) (n = 10) and 3x105/kg (DL3) (n = 16).
Investigators evaluated responses for all 28 patients as of January 26, 2022, after median follow-up of 6.3 months (range, 1.8–29.9). Overall response rate (ORR) for DL1, DL2, and DL3 was 100% (2/2), 80% (8/10), and 93.8% (15/16), respectively. A total of 27 patients were found to be minimal residual disease (MRD) negative using flow cytometry. All (100%) of MRD-assessable patients (27/27) achieved MRD negativity.
“One patient out of 28 could not get assessed. At day 28, 21/24 assessable patients were MRD negative (81.5%), 4/28 patients could not get day 28 MRD assessment follow-up due to COVID-19 restrictions however were assessed at a later timepoint,” investigators reported. “To date best response is MRD- [stringent complete response] in 21/28 patients (75.0%) across all dose levels.”
The safety profile was considered favorable across dose levels. Instances of cytokine release syndrome (CRS) were majority low-grade (grade 0, n = 3 [10.7%], grade 1-2, n = 23 [82.1%], grade 3, n = 2 [7.1%], no grade 4/5), and no instances of immune effector cell-associated neurotoxicity syndrome were reported. CRS median duration measured 3 days (range, 1–8 days). Investigators continue to monitor for duration of response and safety.
“BCMA-CD19 dual FasT CAR-T GC012F continues to provide deep and durable responses with a favorable safety profile in additional RRMM patients across all dose levels demonstrating a very high MRD negativity rate including in pts refractory to anti-CD38, PI, and IMIDs,” investigators concluded. “GC012F is currently being studied in earlier lines of therapy as well as additional indications.”
