samuraciclib (CT7001) / Carrick Therap - LARVOL DELTA

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

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

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

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

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

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 | N=510 ➔ 316

Enrollment change • 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

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 | Recruiting ➔ Active, not recruiting | N=67 ➔ 11 | Trial completion date: Jan 2027 ➔ Nov 2025 | Trial primary completion date: Jul 2026 ➔ Nov 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

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 | Active, not recruiting | Sponsor: Carrick Therapeutics Limited | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

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 completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor 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=510 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Nov 2027

Trial 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

Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Pos/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Prelim Phase 1b Results (SABCS 2024) - P1/2 | "All pts (100%) received prior CDK4/6 inhibitors (ribociclib [n=8], palbociclib [n=7], and abemaciclib [n=1]), 14 (88%) prior aromatase inhibitors, 11 (69%) prior chemotherapy, and 5 (31%) prior fulvestrant. The safety profile of vepdegestrant plus abemaciclib in pts with ER+/HER2- advanced or metastatic breast cancer was generally consistent with the known profiles of each agent, and no DLTs were observed. Neutropenia was manageable with dose modifications. The impact of vepdegestrant on abemaciclib exposure was minor and indicated no significant drug interaction."

Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Cyclin-dependent kinase 7 (CDK7) inhibitor samuraciclib combined with selective estrogen receptor degrader (SERD) elacestrant in advanced HR+ breast cancer after CDK4/6i: dose escalation data from the Phase 1b/2 SUMIT-ELA study (SABCS 2024) - P1/2 | "Samuraciclib (CT7001), a once-daily oral CDK7 inhibitor, combined with the SERD fulvestrant had a favorable safety profile and clinical activity in patients with HR+/HER2− advanced breast cancer (BC) previously treated with a CDK4/6i [Coombes, 2023]. The most frequent treatment-related AEs were similar to the known safety profiles from both previous samuraciclib and elacestrant studies. With no drug-drug interactions between the treatments, further study of combination treatment in expansion C4 is supported. Preliminary signs of antitumor activity were observed."

Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK7 • ER • HER-2 • TP53

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 | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

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

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 | Active, not recruiting | Sponsor: Carrick Therapeutics Limited | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • TP53

Fulvestrant with or without the cyclin-dependent kinase 7 (CDK7) inhibitor samuraciclib in advanced hormone receptor positive (HR+) breast cancer after CDK4/6 inhibition: Phase II SUMIT-BC study. (ASCO 2024) - P2 | "Coombes et al. Nature Comms 2023."

Metastases • P2 data • Breast Cancer • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK7 • ER • HER-2

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=67 | Recruiting | Sponsor: Pfizer | Trial completion date: Aug 2027 ➔ Jan 2027 | Trial primary completion date: Feb 2027 ➔ Jul 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation