During the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Gracell Biotechnologies shared extended follow-up data from a multicenter study that assessed the effectiveness of GC012F in patients with relapsed/refractory multiple myeloma (RRMM). The data was presented in the form of an oral abstract session (abstract #8005).

GC012F represents an innovative candidate in the field of CAR-T therapy, poised to redefine the boundaries of autologous CAR-T treatment in various aspects such as enhanced manufacturing speed, improved safety, cost-effectiveness, and prolonged effectiveness. GC012F is currently being evaluated across three hematological malignancies, including R/R MM, newly diagnosed multiple myeloma, and R/R B-NHL.

In the single-arm, open-label, multicenter investigator-initiated trial (IIT), 29 RRMM patients were enrolled and treated with GC012F. It took place between October 2019 and January 2022. The patients received GC012F at three different dose levels: 1×10⁵, 2×10⁵, and 3x10⁵ cells/kg. Before the trial, the patients had undergone a median of five lines of therapy (ranging from 2 to 9), and 97% of them had received treatment with immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies. Furthermore, 90% of the patients were classified as high-risk according to mSMART 3.0 criteria.

As of the data cutoff date of April 12, 2023, and with a median follow-up period of 30.7 months (ranging from 14.6 to 43.6 months), patients who received GC012F achieved the following outcomes:

• GC012F treatment resulted in an overall response rate (ORR) of 93.1% (n=27/29), with 89.6% (n = 26/29) achieving a very good partial response (VGPR) or better;
• A total of 82.8% (n = 24/29) of patients attained a minimal residual disease (MRD) negative stringent complete response (sCR);
• 100.0% (n = 29/29) of treated patients achieved MRD negativity.
• Median time to best response: 3 months (range 0.9-15.3)

GC012F showcased long-lasting responses in a patient population primarily composed of individuals with a high-risk profile:

• The median duration of response (DOR) was 37.0 months;
• Median progression-free survival (PFS) was 38.0 months;
• Patients who maintained MRD negativity for 12 months experienced an extended PFS;
• 34% (n = 10/29) maintained a stringent complete response (sCR) with minimal residual disease (MRD) negativity for over 12 months. These patients had a projected PFS rate of 100% at the 36-month.

GC012F continued to show a favorable safety profile:

• During the extended follow-up period, no new safety concerns were identified, and specifically, there were no instances of neurotoxicity reported;
• There were no reports of additional primary malignancies identified;
• The majority of cases of cytokine release syndrome (CRS) were of low grade (Grade 1/2: 79%). Two patients (2 out of 29, 7%) experienced Grade 3 CRS but recovered swiftly following standard-of-care treatment. No instances of Grade 4 or 5 CRS events were observed;
• There were no cases of neurotoxicity or immune effector cell-associated toxicity (ICANS) observed at any grade.

KOL insights

“Empowered by the BCMA/CD19 dual-targeted approach and the FasTCAR-T next-day manufacturing technology, GC012F showed impressive clinical outcomes in a challenging patient population. We are highly encouraged by the depth and durability of responses shown in this study” –Expert Opinion.

“A third of patients with sustained MRD-negativity, all of whom still ongoing with responses at 36 months. Impressive data! Turnaround time unclear though manufacturing appears to be accelerated” –Expert Opinion.

Conclusion

GC012F is developed based on the Gracell’s FasTCAR next-day manufacturing platform which presents several notable benefits such as decreased waiting periods for patients, cost reduction, and improved fitness of T-cells. FasTCAR-T cells are younger and exhibit increased proliferation and tumor clearance capabilities in preclinical investigations with reduced ex vivo culture period, allowing for lower cell dose and eliminating the need for ex vivo expansion. The latest findings revealed that GC012F continues to deliver profound and long-lasting responses, along with an exceptionally high rate of MRD negativity in patients with RRMM, even in those who were unresponsive to anti-CD38, PIs, and IMIDs. Given these encouraging results from the GC012F study in RRMM, further clinical investigations will be carried out to validate its effectiveness. The company-sponsored Phase I/II clinical trial in China focused on assessing GC012F in patients with RRMM, is anticipated to commence in the third quarter of 2023.

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