samuraciclib (CT7001) / Carrick Therap - LARVOL DELTA

Interim analysis (IA) of the giredestrant (G) + samuraciclib (SAMURA) arm in MORPHEUS breast cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with oestrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC) (ESMO 2024) - P1/2 | "Circulating tumour DNA was used to define genetic alterations. As of 16 October 2023, 18 and 15 pts were enrolled in the G and G + SAMURA arms, respectively; all had ECOG PS 0–1, 66.7% and 33.3% had prior fulvestrant and 72.2% and 46.7% (capped at 7 pts in the G + SAMURA arm) had liver metastasis at enrolment. Safety of G + SAMURA was aligned with the individual safety profile of each drug, with no overlapping toxicities or new safety signals. Updated data, including efficacy and biomarkers, will be presented."

Clinical • Metastases • P1/2 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 • CDK7 • ER • HER-2

Samuraciclib for the Treatment of Patients With Resectable, Borderline Resectable, or Locally Advanced Basal Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • GATA6 • HMGA2

Samuraciclib for the Treatment of Patients With Resectable, Borderline Resectable, or Locally Advanced Basal Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: University of Washington | Initiation date: Jul 2026 ➔ Oct 2026

Trial initiation date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • GATA6 • HMGA2

SONIC: Samuraciclib in Combination With Gemcitabine/Nab-Paclitaxel in Patients With Metastatic Basal-Like Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=67 | Not yet recruiting | Sponsor: University Health Network, Toronto

New P1/2 trial • Oncology • Pancreatic Cancer • Solid Tumor

CLIP-TAC: A Novel Proteolysis-Targeting Degrader of BCL-XL in Multiple Myeloma (EACR 2026) - "Aims: To overcome thrombocytopenia, a proteolysis-targeting-chimera (PROTAC), called DT2216, was developed that couples navitoclax (BCLXL binder) to a von Hippel–Lindau (VHL) E3 ligase-recruiting ligand to selectively degrade BCLXL in tumour cells, while sparing platelets that lack VHL...Degradation was rescued by pre-treatment with A-1331852 (BCLXL inhibitor) or MLN-4924 (NEDD8-activating enzyme inhibitor), confirming on-target, proteasome-dependent activity...Co-targeting this compensation, either directly with MCL-1 inhibitor AMG-176 or indirectly with cyclin-dependent kinase inhibitors (CYC065, THZ1, Samuraciclib), synergistically enhanced DT2216-induced cell death... MM exhibits heterogeneous dependence on BCL-2 family proteins. BH3-profiling can identify BCLXL-reliant tumours. Targeted degradation of BCLXL with DT2216, or a novel Clip-TAC, shows therapeutic potential in MM."

Hematological Malignancies • Multiple Myeloma • Plasmacytoma • Targeted Protein Degradation • Thrombocytopenia • Von Hippel-Lindau Syndrome • BCL2 • BCL2L1

Samuraciclib for the Treatment of Patients With Resectable, Borderline Resectable, or Locally Advanced Basal Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: University of Washington

New P1 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • GATA6 • HMGA2

C4891024: TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C) (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Apr 2026 ➔ Dec 2026 | Trial primary completion date: Apr 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Epigenetic reprogramming of stromal-epithelial crosstalk to improve immunotherapy response in pancreatic ductal adenocarcinoma (AACR 2026) - "In an orthotopic PDAC mouse model, CT7001 combined with Gemcitabine significantly extended survival. Ongoing spatial multiplex imaging and RNA-seq analyses aim to correlate in vivo immune and stromal changes with in vitro findings, supporting rational combination strategies. This epigenetic screening platform provides a predictive framework to evaluate compounds that overcome CAF-mediated immune exclusion and modulate the tumor microenvironment, offering new avenues to enhance PDAC responsiveness to diverse immunotherapies."

IO biomarker • Stroma • Oncology • Pancreatic Ductal Adenocarcinoma • CAFs

Targeting high risk osteosarcoma: MYC modulation alters metastasis (AACR 2026) - "Nevertheless, the top hit of the screen, samuraciclib, convincingly reverses MYC activity and the associated metastatic phenotype and is undergoing additional testing in metastatic OS mouse models and a canine clinical trial is under development. Correlative biology such as spatial transcriptomics will be used to guide the translation of samuraciclib to patients with high risk osteosarcoma."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • MYC

A potent CDK7 inhibitor TY-2699a suppresses palbociclib-resistant breast cancer and has the potential for combination with chemotherapy or immunotherapy in solid tumors (AACR 2025) - "The efficacy of CT-7001 monotherapy at a dose of 100 mg/kg was comparable to that of TY-2699a at a dose of 1 mg/kg, which only mildly inhibited tumor growth. Our efficacy data of TY-2669a provides a solid rationale for further evaluation of TY-2699a +/- fulvestrant in clinical HR+Her2- CDK4/6-resistant breast cancer patients. In addition, targeted inhibition of CDK7 not only enhanced the efficacy of paclitaxel or gemcitabine in pancreatic cancer cells, but also enhanced the in vivo efficacy of nab-paclitaxel, gemcitabine, and nab-paclitaxel in combination with gemcitabine in mouse pancreatic cancer tumor models...In the single-agent dose escalation stage, TY-2699a showed better clinical safety than SY-5609 did... TY-2699a was more than 80-, 66- and 86-fold more active than palbociclib in palbociclib-resistant stable cell lines of MCF7, T47D and HCC1428 cells, respectively. Consistent with the in vitro results, a 40 mg/kg dose of palbociclib almost completely failed to..."

IO biomarker • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Nasopharyngeal Carcinoma • Oncology • Pancreatic Cancer • Solid Tumor • CDK6 • ER • HER-2

Homogeneous bioluminescent immunoassay for hKi-67 provides a simple and robust screening tool for antiproliferative agents (AACR 2025) - "This assay enables efficient screening of antiproliferative agents, demonstrating exceptional performance in assessing antiproliferative activity across multiple mechanisms of action.We evaluated the Lumit® hKi-67 immunoassay in HCT116 colorectal cancer cells treated with increasing concentrations of four agents known to inhibit proliferation via different mechanisms: palbociclib (CDK4/6 inhibitor), samuraciclib (CDK7 inhibitor), nutlin-3A (MDM2/p53 interaction inhibitor), and thymidine (dNTP pool perturbation). Notably, the Lumit® assay provides faster, more robust data compared to these more labor-intensive alternatives.This study highlights the Lumit® hKi-67 immunoassay as an attractive, high-throughput alternative for screening antiproliferative agents, offering a simpler, faster, and more consistent approach than traditional methods. It is poised to be an invaluable tool in drug discovery and preclinical screening."

Colorectal Cancer • Oncology • Solid Tumor

The liquid biomarker thymidine kinase activity reflecting proliferation rate can provide guidance in drug development and address Project Optimus (AACR 2024) - "After initiation of samuraciclib treatment, a CDK7 inhibitor, a significant reduction in TKa levels in blood from metastatic breast cancer (MBC) patients was observed, indicating inhibition of cell cycle progression...MBC patients monitored >3 months and showing low TKa levels have very low likelihood of progression within 30- to 60 days, <2% and <6%, respectively. TKa is a translational liquid biomarker that bridges results between preclinical and clinical studies, providing fundamental information for drug development decision making."

Biomarker • Breast Cancer • Oncology • Solid Tumor

SUMIT-ELA: A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=49 | Completed | Sponsor: Carrick Therapeutics Limited | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=316 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2027 ➔ May 2029 | Trial primary completion date: Nov 2027 ➔ May 2029

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

Results of the phase 2 SUMIT-BC study, a randomized controlled trial of the cyclin-dependent kinase 7 inhibitor (CDK7i) samuraciclib with fulvestrant in advanced hormone receptor positive (HR+) breast cancer after a CDK4/6 inhibitor (CDK4/6i) (SABCS 2025) - P2 | "Samuraciclib QD combined with fulvestrant demonstrated promising efficacy in ER+/HER2− locally advanced or metastatic BC previously treated using an AI with a CDK4/6i. The most common AEs were dose-related GI AEs. Pharmacokinetics of the new tablet formulation were acceptable."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK7 • ER • HER-2 • TP53

Carrick Therapeutics Announces Positive Results from Phase 2 Randomized Trial of Samuraciclib in Combination with Fulvestrant in Patients with Hormone Receptor Positive, HER2 Negative Advanced Breast Cancer (GlobeNewswire) - "Overall response rate (ORR) of 55% and median progression-free survival of 14.5 months in patients without TP53 gene mutation..'We have achieved clinical proof of concept and look forward to advancing samuraciclib into a Phase 3 clinical trial in 2026 to build on these promising results.'...In the trial, the median PFS of samuraciclib combined with fulvestrant in this TP53wt population was 14.5 months versus 6.8 months with fulvestrant alone, an incremental improvement of 7.7 months."

New P3 trial • P2b data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

CDK7-targeted therapy effectively disrupts cell cycle progression and oncogenic signaling in head and neck cancer. (PubMed, Signal Transduct Target Ther) - "Additionally, CDK7 knockout (KO) and selective inhibitors (YKL-5-124 and samuraciclib) demonstrated potent antitumor activity, effectively suppressing tumor growth in HNSCC patient-derived organoids (PDOs), as well as in both cell line- and patient-derived xenograft (PDX) mouse models with minimal toxicity...These findings highlight CDK7 as a promising therapeutic target for HNSCC. Our study provides strong evidence of the robust antitumor activity of CDK7-selective inhibition in disease-relevant preclinical models, strongly supporting its progression to clinical testing."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDK7

C4891024: TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C) (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Nov 2025 ➔ Apr 2026 | Trial primary completion date: Nov 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Functional insight into cyclin-dependent kinase (CDK)7 via chemical inhibition of the priority fungal pathogen Cryptococcus neoformans. (PubMed, mBio) - "The antifungal activity of SY-1365 was also markedly enhanced in combination with membrane-targeting antifungals. Together, our findings highlight CDK7 inhibitors as valuable tools to study CDK7 function in Cn and as potentially promising antifungals in combination with licensed antifungals."

Journal • CNS Disorders • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Oncology • Transplantation • CDK7

SUMIT-BC: A Study of Samuraciclib in Combination With Fulvestrant in Metastatic or Locally Advanced Breast Cancer in Adult Participants (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Carrick Therapeutics Limited | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2025

Trial completion • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

Resistance to CDK7 inhibitors directed by acquired mutation of a conserved residue in cancer cells. (PubMed, EMBO J) - "Continuous culturing of prostate cancer cells with Samuraciclib, a non-covalent ATP-competitive CDK7i, led to outgrowth of resistant cells...Consistent with this, mutation of the homologous residue in CDK12 (D819N) or CDK4 (D99N) promoted resistance to drugs that inhibit these CDKs. Our findings reveal a general mechanism for acquired resistance with obvious implications for patients treated with CDK inhibitors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDK12 • CDK4

SUMIT-BC: A Study of Samuraciclib in Combination With Fulvestrant in Metastatic or Locally Advanced Breast Cancer in Adult Participants (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Carrick Therapeutics Limited | Trial primary completion date: Jun 2025 ➔ Mar 2025

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

Carrick Therapeutics Announces New Clinical Data Supporting Biomarker-driven Patient Selection for Samuraciclib (CDK7i) in Combination with SERDs in Hormone Receptor Positive Advanced Breast Cancer (GlobeNewswire) - "Carrick Therapeutics Inc...today announced results from a new analysis of two Phase 2 clinical trials of samuraciclib...in patients with hormone receptor positive (HR+) advanced breast cancer who had received prior CDK4/6 inhibitor therapy. The MORPHEUS trial evaluated samuraciclib in combination with giredestrant and the Module 2A trial evaluated samuraciclib in combination with fulvestrant....The analysis indicated that study participants with no evidence of a deleterious mutation in the TP53 gene in circulating tumor DNA at baseline or separately, without liver metastases at baseline, experienced extended durations of progression-free survival....Results of the data analysis indicated improved progression-free survival both for patients with no TP53 mutation, compared to those with mutation, and also for patients without liver metastases, compared to those with liver metastases."

Retrospective data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Patient selection biomarkers for CDK7 inhibitor samuraciclib (SAM; CT7001) combined with selective estrogen receptor degrader (SERD) in hormone receptor-positive advanced breast cancer (HR+ ABC) post-CDK4/6 inhibitor (CDK4/6i) (ESMO-BC 2025) - P1/2 | "SAM was administered to patients (pts) with HR+ ABC with fulvestrant (FUL), an intramuscular (IM) SERD, or giredestrant (GIR), a highly potent, non-steroidal, PO SERD, in 2 independent studies: CT7001_001 (NCT03363893) Module 2A and MORPHEUS (NCT04802759) [Coombes et al. These independent studies suggest that patients with no evidence of either TP53 mutation or of liver metastases may preferentially benefit from SAM + SERD. The observed outcomes in this small dataset appear greater than the anticipated prognostic impact of these factors [O'Leary et al. JNCI 2021; Robertson et al."

Biomarker • Clinical • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK7 • ER • TP53

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=510 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Apr 2026 ➔ Nov 2027

Trial primary completion date • 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 • CDK4 • ER