Ibrance (palbociclib) / Pfizer, Amgen - LARVOL DELTA

Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CCND1 • CD5

Risk of venous thromboembolism associated with CDK 4/6 inhibitors and adjuvant hormonal therapy in non-metastatic breast cancer: A systematic review and meta-analysis (ASH 2025) - "More recently, the Introduction of cyclin-dependentkinase 4 and 6 (CDK 4/6) inhibitors, Abemaciclib, Palbociclib, and Ribociclib, has led to new treatment forhigh-risk patients...The comparator group in thisanalysis consisted of patients treated with endocrine therapy alone with aromatase inhibitors (AI),tamoxifen, or fulvestrant... Results from this study show that for adult patients with local and locally advanced breastcancer, there is increased risk of VTE development when treated with CDK 4/6 inhibitors compared totreatment with endocrine therapy alone. Limitations to this analysis include exclusion of metastaticdisease, limited data available on mortality associated with VTE incidence, and varying degrees of patient-specific thromboembolic risk factors. As the use of CDK 4/6 inhibitors in the treatment of breast cancergrows, this information will provide further information for conversations about risks and benefits whenselecting treatment plans."

Metastases • Retrospective data • Review • Breast Cancer • Chronic Kidney Disease • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Respiratory Diseases • Solid Tumor • Venous Thromboembolism • HER-2

Multiarm Phase I study of the cyclin dependent kinase (CDK4/6) inhibitor palbociclib in combination for patients with relapsed and refractory acute leukemias (ASH 2025) - "Four combination arms were studied (in a 28-day cycle): (A)sorafenib 400mg PO BID on D1-28; (B) decitabine 20 mg/m2 IV on D8-17; (C) dexamethasone 40mg on D1-4 & 11-14, and (D) Venetoclax 400 mg on D1-21. While no complete remissions were observed, clinical benefit was noted in severalpts, particularly in combination with HMA. Further evaluation of palbo, especially in earlier lines oftherapy and in combinations for KMT2a-r or FLT3mutAML may be warranted."

Clinical • P1 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Dermatology • Febrile Neutropenia • Infectious Disease • Neutropenia • Respiratory Diseases • T Acute Lymphoblastic Leukemia • ASXL1 • FLT3 • KMT2A • RUNX1 • TP53 • WT1

Cdk6 targeting reverses leukemia in germline cebpa Q83X AML mouse model with CMP-origin transformation (ASH 2025) - "Targeting CDK6 withpalbociclib potently suppressed leukemic progenitors and clonogenicity exclusively in CebpaQ83X cells,demonstrating genetic dependency.This study establishes germline CebpaQ83X drives leukemogenesis through a three-stage pathogenesis:hyperproliferative, C/ebpα-hi LT-HSCs serve as pre-malignant reservoirs with impaired differentiationcapacity; malignant initiation at CMP stage despite GMP-like surface phenotype—resolving the cellularorigin paradox; epigenetic rewiring positions Cdk6 as a proliferation hub in arrested CMPs. Critically,palbociclib suppresses LT-HSC/CMP proliferation and leukemic outgrowth, providing the first mechanisticrationale for CDK6-targeted therapy in CEBPA N-ter mutant AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Thrombocytopenia • CDK6 • CEBPA

Final results of a phase I/II trial of palbociclib and CPX-351 in patients with Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Toxicities were consistent with those expected from CPX-351 and manageable with supportive care.ConclusionsThe combination of palbociclib and CPX-351 was safe and showed efficacy as frontline treatment fornewly diagnosed AML, including those with R/R AML and adverse risk features. These results support thecontinued evaluation of CDK4/6 inhibition as a combination strategy in AML."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Nephrology • Neutropenia • Respiratory Diseases • Septic Shock • Thrombocytopenia • FLT3 • IDH1 • TP53

Palbociclib combined with venetoclax and azacitidine in NUP98-rearranged pediatric AML: A multicenter phase II trial demonstrating durable remission and survival benefit (ASH 2025) - P1/2 | "It achieved high rates of durable remission at morphological,immunophenotypic, and molecular levels, offering promising long-term survival outcomes. This regimencould become a new standard of care for this high-risk subgroup, potentially redefining frontline therapy,although larger studies with longer follow-up are needed to confirm these findings."

Clinical • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pediatrics • Pneumonia • Respiratory Diseases • CDK6 • KDM5A • NSD1 • NUP98 • TOP1

Cell cycle dependent and independent regulation of AKT activity in germinal center B-cell-like diffuse large B-cell lymphoma – a dual role of cyclin dependent kinase 2 (ASH 2025) - "In contrast, palbociclib (CDK4/6 inhibitor) did not haveany significant AKT inhibitory effect...The PTEN inhibitor HOpic (PTENi) is able to increase AKT activitywithin minutes, but the PTENi-induced increase of AKT activity was completely eliminated by CDK2inhibition (AZD-5438 - CDK1/2/9 inhibitor)...Additionally,CDK2 seems to be involved in a critical feed-forward AKT activation loop. PTEN deletion leads to easierG1-S transition on the Background of increased AKT and metabolic activity.Supported by MHCR (DRO - VFN00064165), National Institute for Cancer Research (EXCELES -LX22NPO5102), and MEYSCR (Cooperatio, SVV 260637)."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CCNA2 • CDK1 • CDK2

CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis (ASH 2025) - "We hypothesized that by protecting HSPCs from the cytotoxic effects of chemotherapy,trilaciclib might also reduce the clonal expansion of TP53-mutant CH during chemotherapy.We obtained serial blood samples from healthy controls (n=176) and three placebo-controlledrandomized clinical trials of trilaciclib including patients with (1) SCLC (n=65) receiving carboplatin andetoposide, (2) metastatic colorectal cancer (mCRC) (n=125) receivingleucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) plus bevacizumab, and (3) metastatic triplenegative breast cancer (mTNBC) (n=34) receiving gemcitabine and carboplatin...Similar effectswere seen with the oral CDK4/6 inhibitor palbociclib and using a dominant negative form of CDK6introduced into p53 mutant HSPCs.Single cell RNA-seq of chimeric mice treated with carboplatin with trilaciclib or single agent controlsrevealed that CDK4/6 inhibition treatment promotes HSC and myeloid progenitor quiescence whilemitigating the myeloid..."

Breast Cancer • Colorectal Cancer • Eye Cancer • Hematological Malignancies • Lung Cancer • Retinal Disorders • Retinoblastoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • PTPRC • TP53

Results of part 1 of a two-part study evaluating the combination of tazemetostat and CPX-351 (part 1) and palbociclib with CPX-351 (part 2) for the treatment of relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - "Inpreclinical studies, AML cell lines treated with the combination of an EZH2 inhibitor (EZH2i) anddoxorubicin exhibited increased DNA damage and apoptosis compared to those treated with doxorubicinalone...Similar levelsof H3K27me3 and DNA-damage were observed at TAZ dose levels 1 and 2, suggesting that no additionalbiologic activity was observed at the higher dose level. Dose level 1 has been selected as therecommended Part 3 dose."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • TAFAZZIN

NUP98::NSD1 fusion is associated with poor outcomes in Acute Myeloid Leukemia regardless of co-occurring mutations and treatment regimen (ASH 2025) - "Three distinct interventions (GO exposure, HCT in first CR (CR1) and sorafenib treatment for ITD+ wereevaluated for potential efficacy in this high-risk cohort. Patients with NUP/NSD AML have dismal outcomes with no improvement in survival withinterventions that have been shown to be effective in other patient subsets. Even those who achieve anMRD negative CR had poor outcomes, suggesting that initial response is not predictive of eventualoutcome. Lack of benefit with HCT in CR1 is particularly concerning."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • NSD1 • NUP98 • WT1

BI14 Case series: exploring the link between psoriasis and cyclin-dependent kinase 4/6 inhibitors in breast cancer treatment. (PubMed, Br J Dermatol) - "She was initiated on palbociclib and letrozole treatment in April 2024...She was commenced on ribociclib and letrozole for relapsed metastatic liver disease in April 2023...Understanding the role of CDK4/6 inhibition and the link with psoriasis is important for optimizing therapeutic choices for patients with cancer with pre-existing or newly developed psoriasis. Given the increasing use of CDK4/6 inhibitors in cancer treatment, clinicians should be vigilant of the potential increased prevalence of psoriasis experienced in this patient cohort."

Journal • Breast Cancer • Dermatology • Dermatopathology • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Psoriasis • Solid Tumor • ER • HER-2 • IL17A • IL22

A study of aumolertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS mutations (APEAK) (ESMO Asia 2025) - P1/2 | "Background: Although KRASG12C-specific inhibitors (KRASG12Ci) like sotorasib show efficacy in KRASG12C-mutated NSCLC, therapeutic resistance remains challenging. Clinical Trial Identification. NCT06947811."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Pharmacokinetics (PK), safety, and tolerability of lasofoxifene in healthy Chinese female adults: results from an open-label, single-dose phase I study (ESMO Asia 2025) - P | "LAS monotherapy was more effective than fulvestrant monotherapy at inhibiting tumour growth in mice bearing human breast carcinoma xenografts harbouring activating estrogen receptor 1 mutations, and so was LAS plus palbociclib versus fulvestrant plus palbociclib. There was no marked difference in drug exposure between premenopausal and postmenopausal healthy Chinese female adults following one dose of oral LAS 5 mg. No clinically relevant differences in PK of LAS were observed for the Chinese healthy females in this study when compared cross-trial to data from Japanese and Caucasian healthy females. LAS was safe and well tolerated."

Clinical • P1 data • PK/PD data • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Cyclic kinase 4 and 6 inhibitor plus endocrine therapy (ET) as first-line therapies in advanced breast cancer: A patient-level data network meta-analysis (ESMO Asia 2025) - "In the first-line setting for HR+/HER2− advanced breast cancer, all CDK4/6 inhibitors combined with endocrine therapy significantly improve progression-free survival compared with endocrine therapy alone, with no significant differences observed among them."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Genomic testing and survival outcomes in metastatic breast cancer: A retrospective study from western India (ESMO Asia 2025) - "Among HR+ patients, 64.2% (318/495) received hormonal therapy, including Palbociclib/Ribociclib in n=115 cases; 62.8% (183/292) of HER2+ patients received targeted therapy. Enhancing access to genomic testing and targeted therapies, along with strengthening real-world data and integrating precision oncology into routine practice, are crucial for optimizing outcomes in metastatic breast cancer."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • FGFR2 • HER-2 • TP53

The activity of SIM0270 alone or in combination with everolimus or palbociclib in ER-positive, HER2-negative breast cancer patients with brain metastases (ESMO Asia 2025) - P1 | "Observed encouraging clinical benefits support further investigation for the use of SIM270 in combination with palbociclib or everolimus in ER-positive, HER2-negative breast cancer patients with BM."

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Efficacy of abemaciclib following progression on prior CDK4/6i in HR+/HER2- metastatic breast cancer: Real-world experience in Moscow (ESMO Asia 2025) - "Of these, 23 patients had previously progressed on first line palbociclib (n=12) or ribociclib (n=11) and were subsequently treated with abemaciclib plus fulvestrant. Median age was 62 years (range: 31–88). Our real-world data support the use of abemaciclib after progression on other CDK4/6i. The observed clinical benefit is consistent with previously published data from the postMONARCH study and other retrospective series. Sequential use of CDK4/6i may be a valuable treatment strategy for selected patients with sustained endocrine sensitivity, delaying the need for chemotherapy."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Concomitant use of proton pump inhibitors and palbociclib or abemaciclib in patients with endocrine-sensitive advanced breast cancer: A multicenter retrospective study (ESMO Asia 2025) - "Concomitant PPI use decreased the effectiveness of palbociclib; however, it did not affect the effectiveness of abemaciclib."

Metastases • Retrospective data • Breast Cancer • Oncology • Solid Tumor • CDK4

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Safety of CDK4/6 inhibitors in older patients: A FAERS-based analysis of serious and fatal adverse events. (PubMed, J Geriatr Oncol) - "Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients."

Adverse events • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A randomized phase II study to evaluate the efficacy and safety of Trastuzumab deruxtecan (T-DXd) versus CDK4/6 inhibitor-based endocrine therapy as first-line therapy of hormone receptor-positive (HR+) and HER2-low/ultralow advanced breast cancer (ABC) patients classified as non-luminal subtype according to gene expression profiling: the PONTIAC study (SABCS 2025) - P2 | "Moreover, pts treated with a CDK4/6 inhibitor in the adjuvant setting with a treatment-free interval ≥ 12 months following CDK4/6 inhibitor treatment completion are allowed.Pre-screening central PAM50 analysis will be conducted in endocrine-resistant pts and in endocrine-sensitive pts who meet at least one of the following criteria: estrogen receptor expression ≤ 50% or presence of liver metastases, or high histological grade or Ki67 > 50% in the primary tumor or known non-luminal subtype as per local PAM50 analysis.Pts will be randomized 1:1 to either T-DXd (5.4 mg/kg intravenously once every 3 weeks) or endocrine therapy (fulvestrant or an aromatase inhibitor ± GnRH analogs for men and pre-/perimenopausal women) plus investigator's choice of CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). Pts-reported outcomes and safety will be analyzed descriptively. Target enrollment is 200 pts, and initial patient enrollment is anticipated to begin in..."

Clinical • Gene expression profiling • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Randomized open-label multicenter phase 2 trial comparing first-line olaparib versus CDK4/6 inhibitor plus endocrine therapy in patients with gBRCAmut-associated HR+/HER2- advanced breast cancer [BR21-08, OPERA trial] (SABCS 2025) - "Six patients received CDK4/6i+ET (2 ribociclib, 2 abemaciclib, 2 palbociclib) and 3 received olaparib as first-line therapy. In gBRCAmut HR+/HER2- ABC, first-line olaparib demonstrated numerically longer PFS and a favorable safety profile compared with CDK4/6i plus ET. These findings should be interpreted with caution given the small sample size."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • HER-2 • HRD

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA

How to prevent and treat cardiovascular diseases in people living with breast cancer? Recent advances. (PubMed, Kardiol Pol) - "CTR-CVT in breast cancer encompasses a wide range of cardiovascular disease and can arise from both traditional anticancer therapies, such as anthracyclines, and newer agents, such as olaparib and palbociclib...We consider the emerging CTR-CVT primary prevention strategies in PLBC and novel markers of subclinical CTR-CVT. Lastly, we consider late CTR-CVT and the importance of long-term surveillance in this cohort."

Journal • Review • Breast Cancer • Cardiovascular • Oncology • Solid Tumor

Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (SABCS 2025) - "Methods SERENA-6, a randomized, double-blind, phase 3 trial, enrolled pts with HR+/HER2- ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (palbociclib/ribociclib/abemaciclib). No new safety signals were observed. These results further support an early switch to CAMI + CDK4/6i during 1L therapy to delay disease progression."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2