New Investigator Sponsored Data Suggest Trilaciclib May Mitigate Chemotherapy-Induced TP53-Mutant Clonal Hematopoiesis
MORRISTOWN, NJ, UNITED STATES, December 7, 2025 /EINPresswire.com/ -- Pharmacosmos Therapeutics Inc. today announced the presentation of new investigator-sponsored research at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. The abstract, titled “CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis” (Abstract #8419), was featured during a Plenary Scientific Session on Sunday, December 7 from 2:00–4:00 p.m. ET.
The study, led by investigators from Washington University in St. Louis and Memorial Sloan Kettering Cancer Center, evaluated whether the intravenous CDK4/6 inhibitor trilaciclib may reduce the expansion of chemotherapy-associated TP53-mutant clonal hematopoiesis (CH), a known risk factor for therapy-related myeloid neoplasms (tMN). Pharmacosmos Therapeutics provided trilaciclib and blood samples from clinical trials with trilaciclib for use in this investigator-sponsored study but did not sponsor or conduct the research.
The research showed that across three placebo-controlled trials involving patients with small cell lung cancer (SCLC), metastatic colorectal cancer (mCRC), and metastatic triple-negative breast cancer (mTNBC), administration of trilaciclib prior to chemotherapy was associated with a significantly lower rate of TP53-mutant CH clone expansion compared to placebo. In preclinical murine models, concomitant treatment with trilaciclib and carboplatin prevented expansion of p53-mutant hematopoietic stem cells, while preserving normal progenitor cells under cytotoxic stress.
Principal investigator and senior author Kelly Bolton, MD, PhD from Washington University in St. Louis, described this trial as “the first time that an approach has been identified to reducing expansion of TP53-mutant CH during therapy. The data generated regarding trilaciclib’s role are emerging across multiple clinical contexts, consistently demonstrating a potential pattern of reduced TP53-mutant CH growth.”
Additionally, co-corresponding author Omar Abdel-Wahab, MD from Memorial Sloan Kettering Cancer Center added that “therapy related myeloid neoplasms are a very troubling complication of cancer therapy. There are currently very limited effective treatments when therapy-related myeloid neoplasms occur. We are very excited about this study, as the results provide the first clue about a strategy to prevent the development of therapy-related myeloid neoplasms.”
These data represent the first demonstration in patients of a pharmacologic strategy that may help limit chemotherapy-induced expansion of pre-leukemic TP53-mutant clones. Further studies are needed to confirm clinical significance.
About Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms
Clonal hematopoiesis (CH) refers to the presence of somatic mutations in hematopoietic stem or progenitor cells that confer a selective growth advantage, leading to clonal expansion with age or under genotoxic stress. Expansion of TP53-mutant clones has been linked to an increased risk of developing therapy-related myeloid neoplasms (tMN), a rare but serious late complication of prior cytotoxic therapy. Currently, there are no approved interventions to prevent CH expansion or reduce the risk of tMN.
About COSELA® (trilaciclib)
COSELA® (trilaciclib) is an intravenously administered cyclin-dependent kinase (CDK) 4/6 inhibitor approved by the U.S. Food and Drug Administration to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). COSELA is not approved for reducing clonal hematopoiesis or preventing therapy-related myeloid neoplasms.
The recommended dose of COSELA is 240 mg/m², administered as a 30-minute intravenous infusion completed within four hours prior to the start of chemotherapy.
Important Safety Information
CONTRAINDICATION
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.
WARNINGS AND PRECAUTIONS
Injection-Site Reactions, Including Phlebitis And Thrombophlebitis
COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.
Acute Drug Hypersensitivity Reactions
COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA.
Interstitial Lung Disease/Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/pneumonitis, and severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA.
Embryo-Fetal Toxicity
Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.
Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).
Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each).
Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA.
The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.
DRUG INTERACTIONS
COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin).
To report suspected adverse reactions, contact Pharmacosmos Therapeutics at 1-800-790-4189 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
This information is not comprehensive. Please see the full Prescribing Information.
About Pharmacosmos Therapeutics
We are a family-owned company innovating in iron metabolism, blood disorders, and cell cycle biology. With 700+ employees globally, we prioritize quality, collaboration, and patient care to drive life-changing treatments.
Forward Looking Statement
This press release includes forward-looking statements, including statements regarding the potential mechanism and investigational use of trilaciclib. Such statements are based on current expectations and assumptions and involve risks and uncertainties that may cause actual results to differ materially. COSELA® (trilaciclib) is approved only to decrease the incidence of chemotherapy-induced myelosuppression in adults receiving certain regimens for extensive-stage small cell lung cancer. The effects of trilaciclib on clonal hematopoiesis or therapy-related myeloid neoplasms have not been established, and COSELA is not approved for these indications.
The study, led by investigators from Washington University in St. Louis and Memorial Sloan Kettering Cancer Center, evaluated whether the intravenous CDK4/6 inhibitor trilaciclib may reduce the expansion of chemotherapy-associated TP53-mutant clonal hematopoiesis (CH), a known risk factor for therapy-related myeloid neoplasms (tMN). Pharmacosmos Therapeutics provided trilaciclib and blood samples from clinical trials with trilaciclib for use in this investigator-sponsored study but did not sponsor or conduct the research.
The research showed that across three placebo-controlled trials involving patients with small cell lung cancer (SCLC), metastatic colorectal cancer (mCRC), and metastatic triple-negative breast cancer (mTNBC), administration of trilaciclib prior to chemotherapy was associated with a significantly lower rate of TP53-mutant CH clone expansion compared to placebo. In preclinical murine models, concomitant treatment with trilaciclib and carboplatin prevented expansion of p53-mutant hematopoietic stem cells, while preserving normal progenitor cells under cytotoxic stress.
Principal investigator and senior author Kelly Bolton, MD, PhD from Washington University in St. Louis, described this trial as “the first time that an approach has been identified to reducing expansion of TP53-mutant CH during therapy. The data generated regarding trilaciclib’s role are emerging across multiple clinical contexts, consistently demonstrating a potential pattern of reduced TP53-mutant CH growth.”
Additionally, co-corresponding author Omar Abdel-Wahab, MD from Memorial Sloan Kettering Cancer Center added that “therapy related myeloid neoplasms are a very troubling complication of cancer therapy. There are currently very limited effective treatments when therapy-related myeloid neoplasms occur. We are very excited about this study, as the results provide the first clue about a strategy to prevent the development of therapy-related myeloid neoplasms.”
These data represent the first demonstration in patients of a pharmacologic strategy that may help limit chemotherapy-induced expansion of pre-leukemic TP53-mutant clones. Further studies are needed to confirm clinical significance.
About Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms
Clonal hematopoiesis (CH) refers to the presence of somatic mutations in hematopoietic stem or progenitor cells that confer a selective growth advantage, leading to clonal expansion with age or under genotoxic stress. Expansion of TP53-mutant clones has been linked to an increased risk of developing therapy-related myeloid neoplasms (tMN), a rare but serious late complication of prior cytotoxic therapy. Currently, there are no approved interventions to prevent CH expansion or reduce the risk of tMN.
About COSELA® (trilaciclib)
COSELA® (trilaciclib) is an intravenously administered cyclin-dependent kinase (CDK) 4/6 inhibitor approved by the U.S. Food and Drug Administration to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). COSELA is not approved for reducing clonal hematopoiesis or preventing therapy-related myeloid neoplasms.
The recommended dose of COSELA is 240 mg/m², administered as a 30-minute intravenous infusion completed within four hours prior to the start of chemotherapy.
Important Safety Information
CONTRAINDICATION
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.
WARNINGS AND PRECAUTIONS
Injection-Site Reactions, Including Phlebitis And Thrombophlebitis
COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.
Acute Drug Hypersensitivity Reactions
COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA.
Interstitial Lung Disease/Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/pneumonitis, and severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA.
Embryo-Fetal Toxicity
Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.
Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).
Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each).
Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA.
The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.
DRUG INTERACTIONS
COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin).
To report suspected adverse reactions, contact Pharmacosmos Therapeutics at 1-800-790-4189 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
This information is not comprehensive. Please see the full Prescribing Information.
About Pharmacosmos Therapeutics
We are a family-owned company innovating in iron metabolism, blood disorders, and cell cycle biology. With 700+ employees globally, we prioritize quality, collaboration, and patient care to drive life-changing treatments.
Forward Looking Statement
This press release includes forward-looking statements, including statements regarding the potential mechanism and investigational use of trilaciclib. Such statements are based on current expectations and assumptions and involve risks and uncertainties that may cause actual results to differ materially. COSELA® (trilaciclib) is approved only to decrease the incidence of chemotherapy-induced myelosuppression in adults receiving certain regimens for extensive-stage small cell lung cancer. The effects of trilaciclib on clonal hematopoiesis or therapy-related myeloid neoplasms have not been established, and COSELA is not approved for these indications.
Cory Steinberg
Pharmacosmos Therapeutic, Inc.
cos@pharmacosmos.us
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