On November 2, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that safety data from the first 18 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) (Press release, G1 Therapeutics, NOV 2, 2022, View Source [SID1234622766]). These initial data highlight the potential for trilaciclib to meaningfully reduce adverse events related to use of sacituzumab.
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"Though the data are preliminary, we are seeing encouraging and consistent reductions in the rate of adverse events related to use of sacituzumab govitecan-hziy when trilaciclib is administered prior to the ADC, relative to the previously published single agent safety profile of this ADC, including those related to myelosuppression," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "We believe we are seeing on-target effects of trilaciclib in the expected reduction in the rate of myelosuppression and in the rates of diarrhea and potentially alopecia. We will continue to progress this trial and look forward to presenting a more comprehensive data set including initial efficacy results at a medical meeting in the second quarter of 2023."
Preliminary Safety Data (n=18): Trilaciclib is well tolerated when administered prior to sacituzumab. Initial data on the first 18 patients show 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, thrombocytopenia), and diarrhea and potentially alopecia due to the presence of CDK4/6-expressing cells in the intestinal crypt and hair follicles.
Summary of treatment-emergent adverse events (TEAEs) (≥ 15% of patients) in patients receiving trilaciclib in combination with sacituzumab govitecan-hziy Summary of TEAEs in patients receiving sacituzumab govitecan-hziy1
(Only includes TEAEs also reported in patients receiving trilaciclib and sacituzumab govitecan-hziy)
Phase 2 trial of trilaciclib in combination with sacituzumab govitecan-hziy TEAEs (n=18) ASCENT TEAEs (no trilaciclib) (n=258)
Adverse Event Any Grade Grade 3-4 Adverse Event Any Grade Grade 3-4
Fatigue 44% 0% Fatigue 52% 4%
Nausea 39% 0% Nausea 62% <4%
Constipation 28% 0% Constipation 37% <1%
Diarrhea 28% 0% Diarrhea 65% 11%
Headache 28% 0% Headache 18% 1%
Neutropenia 22% 17% Neutropenia 64% 52%
Decreased Appetite 22% 0% Decreased Appetite 28% 2%
Leukopenia 17% 17% Leukopenia 17% 10%
1Adapted from Bardia A, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021;384:1529-41. DOI: 10.1056/NEJMoa2028485. Table S1
Summary of other relevant TEAEs in patients receiving trilaciclib in combination with sacituzumab govitecan-hziy Summary of other relevant treatment-related adverse events (TRAEs) in patients receiving sacituzumab govitecan-hziy2
Phase 2 trial of trilaciclib in combination with sacituzumab govitecan-hziy TEAEs (n=18) ASCENT TRAEs (no trilaciclib) (n=258)
Adverse Event Any Grade Grade 3-4 Adverse Event Any Grade Grade 3-4
Anemia 6% 0% Anemia 34% 8%
Febrile Neutropenia 0% 0% Febrile Neutropenia 6% 6%
Thrombocytopenia 0% 0% Thrombocytopenia 5% 2%
2Adapted from Bardia A, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021;384:1529-41. DOI: 10.1056/NEJMoa2028485. Table 3
Phase 2 Trial Design
This is an exploratory Phase 2, multicenter, open-label, single arm study evaluating the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in patients with unresectable, locally advanced or metastatic TNBC who received at least 2 prior treatments, at least 1 in the metastatic setting. Trilaciclib will be administered as a 30-minute IV infusion completed within 4 hours prior to the start of sacituzumab govitecan-hziy treatment on day 1 and day 8 of each 21-day cycle.
The primary objective is to evaluate the anti-tumor efficacy of trilaciclib when administered prior to sacituzumab govitecan-hziy as measured by progression-free survival (PFS). Key secondary endpoints include evaluation of the anti-tumor efficacy as measured by the objective response rate (ORR), duration of objective response (DOR), clinical benefit rate (CBR), and overall survival (OS); and evaluation of the myeloprotective effects of trilaciclib.
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 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.