Meaningful Improvement in Overall Survival (OS) and Tolerability Observed in Patients Receiving Trilaciclib in Combination with a TROP2 Antibody-Drug Conjugate (ADC)
G1 Therapeutics announced Phase 2 trial results showing that trilaciclib, combined with sacituzumab govitecan (SG), extends overall survival (OS) in metastatic triple-negative breast cancer (mTNBC) patients compared to SG alone.
Key findings include a median OS improvement to 15.9 months in the intent-to-treat (ITT) population and up to 17.9 months in a more comparable patient population. Trilaciclib also reduced multiple adverse events like neutropenia, anemia, and diarrhea.
The results will be presented at the 2024 ASCO meeting and support further evaluation in combination trials.
- Median OS improvement to 15.9 months in ITT population.
- Exploratory analysis shows a 48% improvement in median OS to 17.9 months.
- Trilaciclib significantly reduced neutropenia, anemia, and diarrhea rates.
- 12-month OS rate of 60% in ITT population.
- Trilaciclib well-tolerated when administered prior to SG.
- PFS remained unchanged at 4.1 months.
- 23% of patients experienced prior oral CDK4/6 inhibitor treatment, which lowered median OS to 8.0 months in those patients.
- High pre-treatment levels in patients may skew results.
Insights
From a clinical perspective, the Phase 2 trial results for trilaciclib in combination with a TROP2 ADC (sacituzumab govitecan) in patients with metastatic triple negative breast cancer (mTNBC) are quite encouraging. The reported improvements in median overall survival (OS)—from 12.1 months to 15.9 months in the intent-to-treat (ITT) population and up to 17.9 months in a more comparable patient population—are substantial. This is important because OS is a critical endpoint in oncology trials, reflecting how long patients live after starting treatment. The reduction in adverse events, like diarrhea and myelosuppression (neutropenia, anemia, thrombocytopenia), also supports the potential for trilaciclib to improve patient quality of life by making this combination therapy more tolerable. These results suggest that trilaciclib could play a significant role in future treatment regimens for mTNBC.
The approximately six-month improvement in OS for patients receiving trilaciclib in combination with sacituzumab govitecan compared to historical data from the ASCENT trial is impressive. The differentiation between the intent-to-treat and the more comparable patient population highlights the robustness of the data and underscores the importance of patient selection in clinical trials. Moreover, the reduction in treatment-emergent adverse events (TEAEs) aligns with the mechanism of action of trilaciclib, which is known to protect against certain side effects of chemotherapy. This could pave the way for this combination therapy to be a new standard of care, pending further validation in larger pivotal trials.
For retail investors, these new clinical results are a significant milestone for G1 Therapeutics. A six-month improvement in median overall survival (OS) in a difficult-to-treat cancer like mTNBC could potentially position trilaciclib as a valuable addition to current therapy options. Short-term, we might see increased investor interest and stock price appreciation as the market reacts to this positive data. Long-term, if these results are confirmed in larger pivotal trials, trilaciclib could expand its market, providing a recurring revenue stream for G1 Therapeutics. The reduction in adverse events also means fewer complications and potentially lower healthcare costs, which are attractive attributes for gaining adoption among healthcare providers. Investors should keep an eye on upcoming presentations and further clinical developments to gauge the full potential of this combination therapy.
- 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
“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:
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 alone based on historical data from the ASCENT trial. Twelve-month OS was
60% . - Since the conclusion of the ASCENT trial, the treatment landscape has evolved and T-DXd has since been approved for use in patients with HER2-low disease. Given that it was not an approved indication for T-DXd at the time of ASCENT, an analysis was conducted to exclude patients who received subsequent anticancer therapy (SACT) with T-DXd by censoring patient data from the start of SACT with T-DXd for those patients who received it. The outcomes in this censored population are potentially more comparable to results from the ASCENT study. In this patient population, median OS among patients receiving trilaciclib was 17.9 months vs. 12.1 for SG alone.
Exploratory Survival Analyses
- All patients were diagnosed with unresectable, locally advanced or metastatic TNBC at the time of study entry. However, in patients who had an initial breast cancer diagnosis of TNBC (n=20), median OS was 17.9 months compared to 12.0 months in those without TNBC as the initial diagnosis.
- In patients who had previously received checkpoint inhibitor therapy with PD-(L)1 inhibitors (n=22), median OS was 18.1 months compared to 11.4 months in patients who did not receive checkpoint inhibitor therapy.
- In patients who did not receive prior oral CDK4/6i therapy (n=24), median OS was 17.9 months compared to 8.0 months in those who did.
In the overall population (N = 30), confirmed CBR was
Safety Data (n=30)
Trilaciclib was well tolerated when administered prior to SG. Mature safety results show a clinically meaningful on-target effect of trilaciclib to reduce the rates of multiple treatment emergent adverse events (TEAEs) associated with SG compared to the previously published SG single agent safety profile from the ASCENT trial, including measures of myelosuppression (neutropenia, anemia, thrombocytopenia) and diarrhea due to the presence of CDK4/6-expressing cells in the intestinal crypt.
| Summary of TEAEs in patients receiving trilaciclib in combination with SG | Summary of TEAEs in patients receiving SG* | |||||||
| Phase 2 trial of trilaciclib in combination with sacituzumab: TEAEs (n=30) | ASCENT (no trilaciclib): TEAEs (n=258) | |||||||
| Adverse Event | Any Grade | Grade 3-4 | Adverse Event | Any Grade | Grade 3-4 | |||
| Diarrhea | Diarrhea | |||||||
| Neutropenia | Neutropenia | |||||||
| Anemia | Anemia | |||||||
| Thrombocytopenia | Thrombocytopenia | |||||||
*Adapted from A Bardia, et al., Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer, N Engl J Med 2021; 384:1529-1541
“These mature Phase 2 results are compelling and will be essential to determining the design of future pivotal combination trials,” said Raj Malik, MD, G1 Therapeutics’ Chief Medical Officer. “In particular, the approximately six-month improvement in OS observed in the patient population that more closely mirrors that of the ASCENT trial indicates an opportunity to meaningfully enhance the therapeutic potential of a TROP2 ADC. We look forward to sharing these data with the medical community at ASCO, and to identifying the right partners to support advancement of this important combination.”
About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15
About G1 Therapeutics
G1 Therapeutics, Inc. is a commercial-stage oncology biopharmaceutical company whose mission is to develop and deliver next-generation therapies that improve the lives of those affected by cancer, including the Company’s first commercial product, COSELA® (trilaciclib). The Company is also evaluating therapies in combination with cytotoxic therapies and/or immunotherapy in areas of high unmet need including triple-negative breast cancer and extensive stage small cell lung cancer. G1’s goal is to provide innovative therapeutic advances for people living with cancer. G1 is based in Research Triangle Park, N.C. For additional information, please visit http://www.g1therapeutics.com and follow us on X (formerly known as Twitter) @G1Therapeutics and LinkedIn.
G1 Therapeutics® and the G1 Therapeutics logo and COSELA® and the COSELA logo are trademarks of G1 Therapeutics, Inc.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," “could”, “believe,” “goal”, “projections,” "estimate," "intend," “indicate,” “potential,” “promising,” “opportunity,” “suggest,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this press release include, but are not limited to, the ability of trilaciclib to significantly reduce the side effect burden associated with this sacituzumab which can meaningfully improve the tolerability of this ADC, and that these are hypothesis-generating Phase 2 results that may, with further testing, change the therapeutic landscape for these patients, are based on the company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the company’s filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein and include, but are not limited to, the company’s dependence on the commercial success of COSELA (trilaciclib); the development and commercialization of new drug products is highly competitive; the company’s ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; the company’s initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a commercial-stage company; and market conditions. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
G1 Therapeutics Contacts:
Will Roberts
Communications Officer
Vice President, Investor Relations and Corporate Communications
(919) 907-1944
wroberts@g1therapeutics.com
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1 Bardia et al. Final Results from the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression." Journal of Clinical Oncology (2024): JCO-23.
FAQ
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