Abstract 201P
Background
Trilaciclib protects CDK4/6-dependent hematopoietic stem and progenitor cells during chemotherapy (CT; myeloprotection). SG is an antibody–drug conjugate indicated to treat pts with mTNBC. In the phase III ASCENT trial, SG significantly extended survival vs single-agent CT but was associated with increased neutropenia (any grade [G], 63% vs 43%; G3/4, 51% vs 33%) and diarrhea (any G, 59% vs 12%; G3/4, 10% vs < 1%; Bardia et al. N Engl J Med. 2021). In a phase II trial of trilaciclib prior to CT in mTNBC, trilaciclib modulated antitumor immunity (Tan et al. Clin Cancer Res. 2022). Administering trilaciclib prior to SG may improve antitumor efficacy and minimize myelotoxicity in pts with mTNBC. We report preliminary safety and efficacy results from a phase II, single-arm trial of trilaciclib in pts receiving SG for mTNBC (NCT05113966).
Methods
Eligible adult pts (≥ 2 prior systemic therapies [≥ 1 in the metastatic setting]; measurable disease; confirmed hormone receptor-/HER2-negative status; ECOG PS 0/1) receive intravenous trilaciclib 240 mg/m2 prior to SG 10 mg/kg on Days 1 and 8 of each 21-day cycle until disease progression/toxicity. Tumor assessments occur at screening, every 6 weeks to week 36, then every 9 weeks until disease progression/subsequent anticancer therapy. Endpoints include antitumor efficacy, myeloprotection, and safety/tolerability.
Results
As of January 17, 2023, 26 (of 45 planned) female pts had been enrolled and completed a median (range) of 4 (2–15) cycles. Pts had received a median of 2 (2–5) prior lines of therapy, including taxanes (n = 20) and immune checkpoint inhibitors (n = 18). See table; objective response rate by PD-L1 status will be presented. One pt had AEs that led to discontinuation of both study drugs.
Table: 201P
| AEs (safety population; N = 26) | Any G, n (%) | G3/4, n (%) |
| Selected AEs by preferred term (PT) FatigueNauseaAlopeciaConstipationDiarrhea Hematological AEs by collapsed PT NeutropeniaAnemiaLeukopenia | -11 (42)10 (39)8 (31)8 (31)8 (31)-6 (23)2 (8)4 (15) | -01 (4)001 (4)-4 (15)03 (12) |
| Best overall response (response-evaluable population; N = 20) | n (%) | 95% CI |
| Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD) Objective response rate (CR + PR) Clinical benefit rate (CR + PR + SD24wks) | 05 (25)*10 (50)5 (25)*5 (25)*7 (35) | -8.7–49.127.2–72.88.7–49.18.7–49.115.4–59.2 |
∗PR, n = 6 (30%); 1 pt with PR continued therapy after PD (21% increase in sum of longest diameters)
Conclusions
Preliminary data suggest trilaciclib prior to SG has the potential to reduce the rate and severity of multiple AEs compared with results from trials of SG alone, and warrant its continued evaluation.
Clinical trial identification
NCT05113966.
Editorial acknowledgement
Medical writing assistance was provided by Philip Reardon, PhD, from Alligent Europe (Envision Pharma Group), funded by G1 Therapeutics, Inc.
Legal entity responsible for the study
G1 Therapeutics, Inc.
Funding
G1 Therapeutics, Inc.
Disclosure
L. Seneviratne: Financial Interests, Personal, Invited Speaker, Payment or honararia for lectures, presentations, speakers bureaus, manuscript writing or educational event: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca. K.K. Harnden: Financial Interests, Personal, Invited Speaker: Merck, Daiichi Sankyo, AstraZeneca, Seagen, Eisai. M. Mardones: Financial Interests, Personal, Other, Gilead Sciences Payments for consultant work: Gilead Sciences. M.A. Danso: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Immunomedics, Seattle Genetics; Financial Interests, Personal, Other, Honoraria: Amgen. D. Berz: Financial Interests, Personal, Other, Consulting fees: Jazz Pharma, Sun Pharma; Financial Interests, Personal, Invited Speaker: Jazz Pharma, Sun Pharma, Mirati, EMD Serono, Caris Life Science, AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Jazz Pharma, Sun Pharma, Mirati, EMD Serono, Caris Life Science, AstraZeneca. J. O'Shaughnessy: Financial Interests, Personal, Advisory Role: AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Synthon; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Synthon. D. Patt: Financial Interests, Personal, Invited Speaker: Ideology, Pfizer, DSI; Financial Interests, Personal, Member of the Board of Directors: ASCO; Financial Interests, Personal, Leadership Role: Community College Alliance. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. A. Beelen: Financial Interests, Institutional, Funding, Funding to support all aspects of the study: G1 Therapeutics Inc.; Financial Interests, Personal, Stocks/Shares: G1 Therapeutics Inc.; Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics Inc. T. Oyekunle: Financial Interests, Institutional, Funding, Funding to support all aspects of the study: G1 Therapeutics Inc.; Financial Interests, Personal, Stocks/Shares: G1 Therapeutics Inc.; Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics Inc. V. Dell: Financial Interests, Institutional, Funding: G1 Therapeutics Inc.; Financial Interests, Institutional, Other, Medical writing: G1 Therapeutics Inc.; Financial Interests, Personal, Stocks/Shares: G1 Therapeutics Inc.; Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics Inc. S.A. Hurvitz: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other: Roche, Pfizer; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: Ideal Implant; Financial Interests, Personal, Invited Speaker, An Immediate Family Member: ROM Tech; Financial Interests, Personal, Funding, Honoraria: Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Funding: Genentech/Roche, Novartis, GlaxoSmithKline, Sanofi, Pfizer, Amgen, OBI Pharma, Puma Biotechnology, Dignitana, Bayer, Biomarin, Lilly, Merrimack, Cascadian Therapeutics, Seattle Genetics, Daiichi Sankyo, Macrogenics, Ambryx, Immunomedics, Pieris Pharmaceuticals, Radius Health, Arvinas, Zymeworks, Gilead Sciences, Phoenix Molecular Designs, CytomX Therapeutics, Samumed, Dantari, Orin, Greenwich LifeSciences, AstraZeneca/Daiichi Sankyo, G1 Therapeutics. All other authors have declared no conflicts of interest.