GTHX - Meaningful Improvement in Overall Survival (OS) and Tolerability Observed in Patients Receiving Trilaciclib in Combination with a TROP2 Antibody-Drug Conjugate (ADC) | Benzinga
- New Positive Phase 2 Results in Metastatic Triple Negative Breast Cancer (mTNBC) Indicate That Use of Trilaciclib in Combination with a TROP2 ADC May Be Associated with Improved Median OS Compared to Historical Data for the ADC Alone -
- Exploratory Analysis of a More Comparable Patient Population Showed an Approximately Six-Month Improvement in Median OS Among Patients Receiving Trilaciclib in Combination with the ADC Compared to Historical ADC Data -
- Prolonged OS Observed in Patients Receiving Trilaciclib with Prior Anti-PD-(L)1 Therapy and No Prior Oral CDK4/6 Inhibitor -
- On-Target Effect of Trilaciclib Reduces Rates of Multiple Adverse Events Associated with the TROP2 ADC Including Myelosuppression and Diarrhea -
- Results to be Presented at the 2024 American Society of Clinical Oncology (ASCO) Meeting -
RESEARCH TRIANGLE PARK, N.C., May 28, 2024 (GLOBE NEWSWIRE) -- G1 Therapeutics, Inc. (NASDAQ:GTHX), a commercial-stage oncology company, today announced the presentation of mature Phase 2 clinical trial results describing the positive impact of trilaciclib in combination with a TROP2 ADC (sacituzumab govitecan; SG) on overall survival (OS) and tolerability compared to SG alone based on historical data from the ASCENT trial1. The poster is being presented during the Breast Cancer-Metastatic poster session at the 2024 American Society of Clinical Oncology (ASCO) meeting, held May 31 to June 4, 2024, and will be made available once the poster is presented on June 2, 2024 on the G1 Therapeutics website here.
The poster entitled, "Trilaciclib Combined with Sacituzumab Govitecan (SG) in Metastatic Triple Negative Breast Cancer (mTNBC): Updated Phase 2 Safety and Efficacy Results" (Seneviratne, L. et al.) (abstract number 1091) describes the mature results from a Phase 2 trial of trilaciclib in combination with SG in patients with mTNBC. These results indicate that patients in the intent-to-treat (ITT) population receiving trilaciclib with the ADC experienced an approximately four-month improvement in median OS (15.9 months vs 12.1 months) compared to that expected from the ADC alone based on historical data from the ASCENT trial and had a 12-month survival of 60%. Further, in an exploratory analysis of a potentially more comparable patient population to that enrolled in the ASCENT trial, a 48% or approximately six-month improvement in median OS (17.9 months vs 12.1 months) was observed in patients receiving trilaciclib in combination with SG compared to historical data from SG alone. Prolonged OS was observed in patients receiving trilaciclib with the ADC who had an initial breast cancer diagnosis of TNBC, prior use of checkpoint inhibitors, and no prior oral CDK4/6 inhibitor use. The poster also describes the significant on-target benefit of trilaciclib in reducing adverse events associated with this ADC, including diarrhea, neutropenia, anemia, and thrombocytopenia. These results support further evaluation of trilaciclib prior to SG or other ADCs and will help determine the design of future pivotal combination trials.
"While the development of therapies for the HER2+ and ER+ spectrum of disease is advancing quickly, TNBC remains an area where we continuously seek to identify important therapeutic signals with improved outcomes that should be further developed in well-controlled pivotal clinical trials," said Lasika Seneviratne, M.D., Chief Medical Officer at Los Angeles Cancer Network and Chief Scientific Officer of the Research Division of the Los Angeles Cancer Network (LACN). "In this trial, trilaciclib significantly reduced the side effect burden – neutropenia and diarrhea in particular – associated with sacituzumab which can meaningfully improve the tolerability of this important therapy. And although cross-trial comparisons should be made with caution, we observed a strong survival signal associated with use of trilaciclib prior to sacituzumab in the ITT population in this trial compared to the historical expectation of the ADC alone, and an even stronger signal in the potentially more comparable data that censored patients who received subsequent therapy with an ADC that was not approved for patients with HER-2 low breast cancer at the time of ASCENT. These are important and consistent hypothesis-generating Phase 2 results that may, with further testing, provide an opportunity to change the therapeutic landscape for patients living with TNBC."
The Phase 2 multicenter, open-label, single arm trial enrolled 30 patients with unresectable, locally advanced or metastatic TNBC who received at least two prior treatments, at least one in the metastatic setting. Trilaciclib was administered as a 30-minute IV infusion completed within 4 hours prior to the start of SG treatment on day 1 and day 8 of each 21-day cycle. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. Key secondary endpoints included overall survival (OS), myeloprotection, and safety/tolerability, as well as objective response rate (ORR), clinical benefit rate (CBR; confirmed complete response, partial response, or stable disease lasting ? 24 weeks from first dose), and duration of response (DOR).
Patient Demographics
Enrolled patients (n=30) received a median of 6.0 cycles of treatment, and median follow-up was 15.0 months. One patient remains on study treatment and 12 patients remain in the study. The median age of patients enrolled in the trial was 56.0 years. This trial included a highly pretreated population of patients: 77% (23 of 30) received 2 or 3 prior systemic anticancer regimens, and 23% (7 of 30) received greater than 3 prior systemic anticancer regimens. A majority (73%; 22/30) of patients received prior PD-(L)1 immunotherapy compared to 29% in the ASCENT trial and 20% (6/30) of patients received prior oral CDK4/6 inhibitor treatment. Sixty-seven percent (67%; 20/30) of patients had an initial diagnosis of TNBC. Thirty percent (30%; 9/30) of patients received subsequent anticancer therapy with fam-trastuzumab deruxtecan-nxki (T-DXd).
Key Survival Analyses (n=30)
- In the overall ITT population, patients receiving trilaciclib prior to SG experienced a median OS of 15.9 months compared to the expected 12.1 months for SG ...