The main purpose of this study is to investigate the safety of LY3405105 in participants with advanced cancer. The study has two parts phase 1a and phase 1b. Participants will only enroll in one part.

Start Date31 Jan 2019

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with LY-3405105

100 Translational Medicine associated with LY-3405105

100 Patents (Medical) associated with LY-3405105

Literatures (Medical) associated with LY-3405105

05 Jan 2024·The Oncologist

A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors

Article

Author: Garralda, Elena ; McNeely, Samuel C ; Ribeiro, Silvia ; LoRusso, Patricia ; Yuen, Eunice ; Schram, Alison M ; Xu, Xiaojian ; Wang, Yi ; Cunningham, Jason ; Bedard, Philippe L ; Urunuela, Arantxa ; Schwartz, Gary K

AbstractBackgroundThis study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors.Materials and MethodsLY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity.ResultsFifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n = 3; 35 mg: n = 3; 25 mg: n = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed.ConclusionThe MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development.ClinicalTrials.gov IdentifierNCT03770494.

01 Sep 2020·Cancer and Metastasis ReviewsQ2 · MEDICINE

CDK7 inhibitors as anticancer drugs

Q2 · MEDICINE

Review

Author: Ali, Simak ; Fan, Hailing ; Sava, Georgina P ; Buluwela, Lakjaya ; Coombes, R Charles

AbstractCyclin-dependent kinase 7 (CDK7), along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs progression through the cell cycle via T-loop phosphorylation of cell cycle CDKs. CAK is also a component of the general transcription factor, TFIIH. CDK7-mediated phosphorylation of RNA polymerase II (Pol II) at active gene promoters permits transcription. Cell cycle dysregulation is an established hallmark of cancer, and aberrant control of transcriptional processes, through diverse mechanisms, is also common in many cancers. Furthermore, CDK7 levels are elevated in a number of cancer types and are associated with clinical outcomes, suggestive of greater dependence on CDK7 activity, compared with normal tissues. These findings identify CDK7 as a cancer therapeutic target, and several recent publications report selective CDK7 inhibitors (CDK7i) with activity against diverse cancer types. Preclinical studies have shown that CDK7i cause cell cycle arrest, apoptosis and repression of transcription, particularly of super-enhancer-associated genes in cancer, and have demonstrated their potential for overcoming resistance to cancer treatments. Moreover, combinations of CDK7i with other targeted cancer therapies, including BET inhibitors, BCL2 inhibitors and hormone therapies, have shown efficacy in model systems. Four CDK7i, ICEC0942 (CT7001), SY-1365, SY-5609 and LY3405105, have now progressed to Phase I/II clinical trials. Here we describe the work that has led to the development of selective CDK7i, the current status of the most advanced clinical candidates, and discuss their potential importance as cancer therapeutics, both as monotherapies and in combination settings. ClinicalTrials.gov Identifiers: NCT03363893; NCT03134638; NCT04247126; NCT03770494.

100 Deals associated with LY-3405105

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 1	CA	Eli Lilly & Co.	31 Jan 2019
Advanced cancer	Phase 1	FR	Eli Lilly & Co.	31 Jan 2019
Advanced cancer	Phase 1	US	Eli Lilly & Co.	31 Jan 2019
Advanced cancer	Phase 1	TW	Eli Lilly & Co.	31 Jan 2019
Advanced cancer	Phase 1	ES	Eli Lilly & Co.	31 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	FR	Eli Lilly & Co.	31 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	ES	Eli Lilly & Co.	31 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	TW	Eli Lilly & Co.	31 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	US	Eli Lilly & Co.	31 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	CA	Eli Lilly & Co.	31 Jan 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03770494 (Pubmed)	Phase 1	HR-positive/HER2-low Solid Tumors	54	LY3405105	rtneyxjsdq(egmgshboru) = pjbbyeobgs tegclytimf (govolcqume )	Negative	02 Aug 2023

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

LY-3405105

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation