Improved Survival and Tolerability with Trilaciclib and TROP2 ADC Combination

G1 Therapeutics, Inc. has presented promising Phase 2 clinical trial results showing the efficacy of trilaciclib combined with a TROP2 antibody-drug conjugate (ADC), sacituzumab govitecan (SG), in treating metastatic triple-negative breast cancer (mTNBC). The findings, shared at the 2024 American Society of Clinical Oncology (ASCO) meeting, highlight improvements in overall survival (OS) and reduced adverse events compared to using SG alone.

Study Overview

This Phase 2 trial enrolled 30 patients with unresectable, locally advanced, or metastatic TNBC, all of whom had received at least two prior treatments in the metastatic setting. Trilaciclib was administered as a pre-treatment before SG on specific days of their 21-day treatment cycles. The study's primary endpoint was progression-free survival (PFS), with key secondary endpoints including OS, myeloprotection, and safety/tolerability. Additional measures were the objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR).

Key Findings

1. Overall Survival Improvement: Patients receiving trilaciclib before SG experienced a median OS of 15.9 months, compared to 12.1 months expected from SG alone, based on historical ASCENT trial data. An exploratory analysis showed that the median OS could extend to 17.9 months when comparing a more similar patient population to the ASCENT trial participants.

2. Survival Benefits with Prior Treatments: Prolonged OS was observed in patients who had an initial breast cancer diagnosis of TNBC, prior checkpoint inhibitor therapy, and no prior oral CDK4/6 inhibitor use. Specific median OS improvements included:
- 17.9 months for patients with an initial TNBC diagnosis vs. 12.0 months for those without.
- 18.1 months for patients previously treated with PD-(L)1 inhibitors vs. 11.4 months for those without.
- 17.9 months for patients without prior CDK4/6 inhibitor therapy vs. 8.0 months for those who had.

3. Safety and Tolerability: Trilaciclib demonstrated a significant reduction in adverse events such as neutropenia, anemia, thrombocytopenia, and diarrhea compared to SG alone. This reduction in side effects suggests that trilaciclib potentially enhances the tolerability of SG.

Patient Demographics

The study's participants had a median age of 56 years and were heavily pretreated, with 77% having received 2-3 prior systemic anticancer regimens. A majority (73%) had prior PD-(L)1 immunotherapy, and 67% had an initial diagnosis of TNBC.

Conclusion and Future Directions

The promising results from this Phase 2 trial indicate that trilaciclib, when combined with SG, may offer significant survival benefits and improved tolerability for patients with mTNBC. These findings support further investigation and potential pivotal trials to confirm the therapeutic advantages of this combination treatment. G1 Therapeutics aims to continue exploring this promising combination to potentially improve treatment outcomes for TNBC patients.

About G1 Therapeutics
G1 Therapeutics is dedicated to developing innovative therapies for cancer patients, with a focus on next-generation treatments. Based in Research Triangle Park, N.C., the company is evaluating therapies like trilaciclib in various cancer settings, including triple-negative breast cancer and extensive-stage small cell lung cancer. Their mission is to improve the lives of those affected by cancer through advanced therapeutic options.

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