G1 Therapeutics, Inc. presented preliminary results from 30 patients enrolled in its ongoing Phase 2, single arm study of trilaciclib administered prior to the antibody-drug conjugate (ADC), sacituzumab govitecan-hziy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). These data highlight the potential for trilaciclib to meaningfully reduce adverse events related to use of sacituzumab. As expected, patients with PD-L1(+) tumors appear to respond earlier than patients with PD-L1(-) tumors.

The Company expects to reach the overall survival (OS) endpoints in the first quarter of 2024. Data generated across multiple preclinical and clinical studies to date show that trilaciclib has the effect on longer term endpoints including OS rather than earlier efficacy measures such as ORR and progression free survival (PFS), consistent with other immunotherapies like checkpoint inhibitors. These results suggest that this is likely due to trilaciclib's immune-mediated mechanism of action that protects the immune system from the initial damage caused by ADC therapy and enhances long term immune surveillance by increasing the generation of certain memory T cells.

This dual benefit may provide important longer-term benefits for patients by improving their ability to generate robust immune responses, particularly when treated with future subsequent therapies. Patient Demographics: As of the data cut date of April 3, 2023, all patients (N = 30) had received at least one dose of any study drug and 93.3% of patients had metastatic disease. Patients received a median (range) of 5.5 (1-20) cycles of treatment, and median follow-up was 5.5 months.

Eleven (11) patients remain on study treatment and 22 patients remain in the study. In addition, a majority (73.3%; 22/30) of enrolled patients had received prior PD-(L)1 immunotherapy and 63.3% of patients had PD-L1(+) tumors. Safety Data (n=30): Trilaciclib was well tolerated when administered prior to sacituzumab.

Safety results showed a clinically meaningful on-target effect of trilaciclib to reduce (>50%) the rates of multiple adverse events compared to the previously published sacituzumab govitecan-hziy single agent safety profile from the ASCENT trial, including myelosuppression (neutropenia, anemia) and diarrhea due to the presence of CDK4/6-expressing cells in the intestinal crypt. Treatment-related adverse events (TRAE) of any grade related to any study drug were reported in 76.7% of patients, the most common of which were fatigue, alopecia, nausea, and diarrhea. Adverse events (AEs) leading to treatment discontinuation of study drug occurred in one patient.

Initial Efficacy Results: With a median follow-up of 5.5 months, the efficacy of trilaciclib prior to sacituzumab in this patient population is preliminary. Initial results to date show that ORR is higher in patients with PD-L1(+) mTNBC (confirmed ORR=35.3%) relative to the overall study population (confirmed ORR=25.0%). To date, one additional patient has experienced an unconfirmed response.

The median Progression Free Survival (mPFS) with trilaciclib plus sacituzumab was 4.1 months. The Company expects to reach the OS endpoints in the first quarter of 2024. This study includes a heavily pretreated patient population, with 73.3% of patients having received prior PD-(L)1 treatment and 26.7% of patients having >3 anticancer regimens.

Prior data from the ASCENT trial have shown a 34.9% ORR in the overall study population, and that patients pretreated with PD-(L)1 therapy show lower initial responses to sacituzumab (28.4% in pretreated patients vs. 37.5% in untreated patients) and a lower mPFS vs the overall population (4.2 months pretreated patients vs. 5.6 months in untreated patients).

One patient in G1's trial to date achieved a partial response (59% reduction in the sum of longest diameters; SLD) after initial progressive disease (21% increase in SLD) with continuation of therapy at the investigator's discretion, as the patient seemed to be deriving clinical benefit with trilaciclib and sacituzumab. This patient was not included in the confirmed response calculation. This type of improvement after continued therapy post-progressive disease has been observed with immunotherapies like checkpoint inhibitors but is not usually associated with cytotoxic therapies alone, further suggesting the potential immunotherapeutic benefit of trilaciclib.