Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Imetelstat

Motesanib diphosphate

Antineoplastic Agents, Immunological

Enzyme Inhibitors

GRN163L will be administered in escalating dose cohorts on Day 1 of each 21-day cycle prior to trastuzumab infusion. Trastuzumab will be a administered day 1 of each 21-day cycle after GRN163L. There will be a 30 minute observation period between the end of the GRN163L infusion and the beginning of the trastuzumab infusion.

GRN163L in combination with trastuzumab

Kathy Miller, MD

A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab.

A Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer

A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer

PK data will be described using means, standard deviations, medians, minimums and maximums.

Telomerase activity data will be described using means, standard deviations, medians, minimums and maximums.

Marrow (and tumor when sufficient sample is available) will be analyzed via flow cytometry to determine cell distribution. Percentage of cells at each cycle will be described using means, standard deviations, medians, minimums and maximums.

HER2 family signaling protein activation will be described using means, standard deviations, medians, minimums and maximums.

Breast Cancer Research Foundation

Geron Corporation

Indiana University

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Stomach Neoplasms

Urinary Bladder Neoplasms

Stomach Cancer

Biliary Tract Cancer

Herbal and Botanical

Cola

In Part A, cohorts of patients with select HER2, HER3, or EGFR alterations will receive increasing doses of BDTX-189. It is expected that up to approximately 70 patients will be enrolled in this dose escalation arm. If an alternative schedule is explored, up to 24 additional patients may be enrolled.

In Part B, patients with a solid tumor harboring specific allosteric HER2 mutations or an HER2 or EGFR exon 20 insertion mutation will receive the recommended Phase 2 dose of BDTX-189. It is expected that approximately 100 participants will be enrolled in this phase 2 portion.

Participants will receive a daily, oral dose of BDTX-189 as part of a 3 week cycle.

BDTX-189

This is a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that have select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study are to:

* Find the recommended dose of BDTX-189 that can be given safely to participants
* Learn more about the side effects of BDTX-189
* Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK)
* Determine the antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

BDTX-189 is an irreversible, small molecular inhibitor that is highly selective versus wild-type EGFR and potent for cancer driver mutations of the ErbB family, including extracellular, transmembrane, and kinase domain allosteric mutations of HER2, as well as EGFR and HER2 exon 20 insertion mutations. These allosteric ErbB mutations are found in 1 - 2 % of most solid tumors and enriched in some cancers with a prevalence of about 2 - 7% such as in non-small cell lung cancer, breast cancer, colorectal cancer, bladder cancer, and endometrial cancer. Currently approved HER2 and EGFR directed therapies are not active against the spectrum of allosteric mutations at relevant and tolerated exposure levels.

This Phase 1/2 multi-center, open-label trial is a first-in-human study that will evaluate BDTX-189 orally administered daily as a single agent in patients with solid tumors harboring select mutations or alterations. The Phase 1 portion is a dose escalation primarily designed to assess the safety and tolerability of BDTX-189 and to determine a recommended Phase 2 dose (RP2D). Phase 1 will focus on patients with a solid tumor with alterations such as:

* Allosteric HER2 or HER3 mutation(s)
* EGFR or HER2 exon 20 insertion mutation(s)
* HER2 amplified or overexpressing tumors
* EGFR exon 19 deletion or L858R mutation

Following selection of the RP2D, a Phase 2 portion will be initiated to further evaluate the clinical activity of BDTX-189. Phase 2 will focus on patients with a solid tumor harboring an:

* Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I)
* EGFR or HER2 exon 20 insertion mutation

Eligible mutations must be determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory.

A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.

MasterKey-01: A Phase 1/2, Open-label, Two-part, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics & Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB Mutations, in Patients w/ Advanced Solid Malignancies

Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.

Objective response rate is defined as the proportion of participants who achieve a confirmed complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state.

Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Duration of response is the time from first documentation of a response to first evidence of progressive disease per RECIST version 1.1 or death. A response is defined as either a complete response (CR; disappearance of all target lesions and non-target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions). Progressive disease is defined by a target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions.

Disease control rate is defined as the proportion of participants achieving: a complete response (CR; disappearance of all target and non-target lesions), partial response (PR; at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD; neither sufficient shrinkage to qualify for a PR nor sufficient increase in lesions) per RECIST version 1.1.

Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1.

Overall survival is the time from first study dose until death from any cause or study discontinuation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer	NCT01265927	Breast Neoplasm...	GRN163L in comb...	18 Years -	Indiana University
A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.	NCT04209465	Solid Tumor	BDTX-189	18 Years -	Black Diamond Therapeutics, Inc.

Spots Global Cancer Trial Database for genes, her2

Every month we try and update this database with for genes, her2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for genes, her2

Every month we try and update this database with for genes, her2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for genes, her2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.