Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Trastuzumab deruxtecan

Capecitabine

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

Participants with HER2-low expressing unresectable and/or metastatic breast cancer who will be treated with trastuzumab deruxtecan and part of the enrolled participants will receive conventional chemotherapy. The participants on conventional chemotherapy will be analyzed exploratory only.

This is a non-interventional study and medication will be administered according to the SmPC as local standard of care and as part of the routine clinical practice.

Trastuzumab (T-DXd) to be administered according to the SmPC.

Conventional therapy (eg. capecitabine, eribulin, gemcitabine, paclitaxel, nab paclitaxel) to be administered according to the SmPC.

Contact for Clinical Trial Information

Principal Investigator

Global Team Leader

Trastuzumab deruxtecan (T-DXd) as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

This non-interventional study will investigate the effectiveness withT-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study.

Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study.

DESTINY Breast Respond HER2-low Europe

A Prospective, Non-interventional Study (NIS) With Trastuzumab Deruxtecan For Patients With HER2-low Expressing Unresectable and/or Metastatic Breast Cancer Accompanied By a Disease Registry of Patients Treated With Conventional Chemotherapy (DESTINY Breast Respond HER2-low Europe)

The PGI-TT is designed to assess the treatment tolerability of the medicine. Participants will rate the bother associated with any treatment-related symptoms based on a 5-point scale ranging from 1 (not at all) to 5 (very much). Higher scores indicate a worse outcome.

The EORTC QLQ-C30 questionnaire is designed to measure cancer patients' physical, psychological and social functions. The EORTC QLQ-C30 scales and single-item scales range in score from 0 to 100. A higher score for the functioning scales and global health status denotes a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Patients with HER2+ unresectable and/or mBC who are prescribed T-DXd and have received a prior anti-HER2 based regimen.

Patients with HER2-low unresectable and/or mBC who are prescribed T-DXd and have received a prior chemotherapy.

None (Observational Study)

AstraZeneca Clinical Study Information Center

This study will collect real-world clinical and patient reported outcomes (PRO) and diary data from eligible patients with documented Human Epidermal Growth Factor Receptor 2 (HER2+) \[globally\] or HER2-low \[North America only\] in routine clinical practice.

This is a multi-center, observational prospective study that will characterize the demographic and clinical characteristics, treatment patterns, effectiveness, tolerability and its management, and patient experience of Trastuzumab Deruxtecan (T-DXd) in a real-world setting. This study is planned to be conducted in several countries and aims to enroll approximately 750 patients eligible patients with HER2+ unresectable and/or metastatic breast cancer (mBC) who has received a prior anti HER2 based regimen in the metastatic setting or in the neoadjuvant or adjuvant setting and has developed disease recurrence during or within 6 months of completing therapy. Approximately 250 eligible patients with HER2-low unresectable and/or mBC who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy will be enrolled into the study in North America only.

The planned duration of patient recruitment is approximately 18 months for HER2+ and approximately 12 months for HER2 low.

An Observational Study of Patients Receiving T-DXd for Treatment of HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer

A Multi-center, Multi-country Prospective Observational Study of Patients Initiating T-DXd in the First or Second Treatment Line for HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Real-world time to next treatment will be evaluated. rwTTNT is defined as the length of time from date of first T-Dxd administration to the date the patient received an administration of their next systemic treatment regimen or to their date of death if there is a death prior to having another systemic treatment regimen.

Treatment patterns will be summarised using summary statistics.

Summary statistics will be used to describe the Demographics and clinical characteristics

The safety and tolerability of T-Dxd through the collection of physician-reported SEIs will be assessed.

The management of SEIs will be characterized.

Real-World Time to Discontinuation of T-DXd will be evaluated. rwTTD is defined as time from index date to the earliest date of T-DXd discontinuation, or death.

Patient-reported tolerability will be evaluated by PGI-TT. Single question asking patients how bothered they were by the side effects of their cancer treatment, ranging from Not at all to Very much.

Patient-reported tolerability will be evaluated by selected items from the NCI PRO-CTCAE. The following items are selected: nausea, vomiting, bloating of the abdomen, shortness of breath, cough, heart palpitations, hair loss, and fatigue, tiredness or lack of energy.

Nausea and vomiting symptoms diary will be assessed based on severity, interference with appetite and usual activities.

AstraZeneca

Carcinoma

Taxane

Ricolinostat

Tubulin Modulators

Antimitotic Agents

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Subject will receive ACY-1215 (ricolinostat) orally once daily for 21 consecutive days (Day 1 to Day 21) at the assigned dose, followed by a 7-day non-dosing period (Day 22 to Day 28). 100 mg/m2 Nab-paclitaxel will be administered intravenously on Days 1, 8, and 15.

An orally active, selective HDAC6 inhibitor. Assigned dosing 80 mg, 120 mg, 180 mg, 240 mg PO, once daily Days 1-21 in a 28-day cycle

ACY-1215

Taxanes are among the most widely used chemotherapy agents in the treatment of breast cancer.

100 mg/m2 30 minute IV infusion Days 1, 8, and 15 in a 28-day cycle

Nab-paclitaxel

Kevin Kalinsky, MD, MS

This is a non-randomized phase 1 trial designed to determine the MTD and evaluate the safety and tolerability of ACY-1215 with nab-paclitaxel. Based on the activity profile of ACY-1215 in breast cancer, corresponding biomarker availability with the HDAC6 MR score, and its potential synergy with taxanes, these data support the rationale for testing the ability of ACY-1215 to improve the response rate for patients with metastatic breast cancer in combination with standard taxane chemotherapy.

Breast cancer is the most common female cancer and the second most common cause of death in women. Women with hormone receptor-negative tumors that are associated with symptomatic visceral metastases, or hormone receptor-positive tumors that are refractory to endocrine therapy require cytotoxic chemotherapy for disease control. The standard of care for patients with metastatic breast cancer includes single agent taxane-based chemotherapy. Combination chemotherapy generally provides higher rates of objective response and longer time to progression, compared to single-agent chemotherapy. However, it is associated with increased toxicity and is of little survival benefit. There remains an unmet need for combination regimens incorporating new, effective and oftentimes less toxic targeted agents together with standard chemotherapy.

ACY-1215 + Nab-paclitaxel in Metastatic Breast Cancer

Multi-center Phase IB Trial of ACY-1215 (Ricolinostat) Combined With Nab-paclitaxel in Unresectable or Metastatic Breast Cancer

The maximum tolerated dose (MTD) combination is defined as the dose combination associated with a target probability of dose limiting toxicity (DLT) of 0.25. A dose-limiting toxicity is defined as the MTD with DLTs defined as any grade 3 non-hematologic toxicities despite maximal supportive care or any grade 4 hematologic toxicity. The MTD will be estimated using the time to event continual reassessment method (TITE-CRM). The TITE-CRM will use an empirical dose-toxicity model, with a sample size of 24. The dose-toxicity model is calibrated such that the method will eventually select a dose that yields between 17% and 33% DLT, which will be the recommended phase II dose (RP2D).

All patients will be evaluable for toxicity from the time of their first treatment with the study drug. Toxicities will be graded based upon CTCAE v4.0.2.

Acetylon Pharmaceuticals Incorporated

National Cancer Institute (NCI)

Columbia University

Reproductive Control Agents

Letrozole

Palbociclib

Onapristone

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

This study has two stages: a dose-finding stage and a dose expansion stage. Stage 1 of the study will utilize a standard 3+3 dose de-escalation design with a total of three dose levels of onapristone ER, 30mg PO BID, 40mg PO BID, and 50mg PO BID given on a 28-day cycle. Onapristone ER will be given in addition to letrozole 2.5mg QD and each patient's pre-enrollment dose of palbociclib.

Letrozole will be given daily on days 1-28.

Palbociclib will be given daily on days 1-21 and held on days 22-28, as per standard FDA-approved dosing guidelines.

Onapristone will be given daily on days 1-28.

Onapristone ER

Komal Jhaveri, MD

The researchers are doing this study to find out whether the study drug onapristone ER, combined with the standard treatment for your cancer (letrozole and palbociclib), is a safe treatment for people who have metastatic or unresectable ER+/PR+/HER2- breast cancer. The researchers will test different doses of the study drug to find the highest dose that causes few or mild side effects.

This is an open label, single institution pilot phase 1b study of the oral progesterone antagonist, onapristone ER (Apristor), used as triplet escalation therapy patients with ER+/PR+/HER2- MBC who do not achieve mCR after six months (+/- 4 weeks) of treatment with letrozole and palbociclib in the first line.

A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer

ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study With Letrozole, Palbociclib and Onapristone ER

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The RP2D/MTD will be defined as the dose level at which a dose limiting toxicity (DLT) occurs in at most 1 out of 6 patients in that dose cohort.

Context Therapeutics Inc.

Memorial Sloan Kettering Cancer Center

Rare Diseases

Breast Neoplasms, Male

Breast Cancer, Male

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Interferons

Pertuzumab

Interferon-gamma

Antiviral Agents

Phase 1: Participants with HER-2 positive metastatic breast cancer enrolled in groups of 3-6 or more; each group participant to be given the same dose and schedule of Interferon-gamma plus paclitaxel, trastuzumab, and pertuzumab. If group participants do not have bad side effects, the next group will be given a higher dose of Interferon-gamma. This will continue until the highest safe dose of Interferon-gamma is found. Once highest safe dose of Interferon-gamma is found, participants may be enrolled in Phase II.

Phase 2: Approximately 31 participants with Stage 2-3 HER2 positive early stage breast cancer enrolled to receive therapy with Interferon-gamma plus paclitaxel, trastuzumab, and pertuzumab. Interferon-gamma given at dose found in the Phase 1.

Phase 2: Post therapy surgery.

Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks.

Interferon-gamma (IFN-γ)

Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 2: Participants will be assessed for surgery following the fourth cycle of study therapy (or earlier if study treatment is cancelled due to unmanageable side effects).

Post Therapy Surgery

(Hyo) Heather S. Han, M.D.

This purpose of this study is to evaluate the safety and to find the optimal dose in participants with human epidermal growth factor receptor 2 (HER2) positive breast cancer who are given the combination of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab. This study will also look at other effects of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab, including its effect on this type of cancer.

Interferon-gamma is a biologically manufactured protein that is similar to a protein the body makes naturally. In the body, interferon gamma is produced by immune cells and helps to prevent serious infections.

Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer

A Phase I-II Study of Interferon-gamma Plus Weekly Paclitaxel, Trastuzumab and Pertuzumab in Patients With HER-2 Positive Breast Cancer

The dose limiting toxicity (DLT) evaluation period for dose escalation will be during the first three weeks. The maximum tolerated dose (MTD) dose level is defined as the highest dose level with ≤1 out of 6 participants experiencing a DLT. If the first dose level experience two or more DLTs, then dose de-escalation will occur. DLT during cycle one (C1) is defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 in severity and probably or definitely related to study therapy which leads to chemotherapy treatment delays \> 14 days are considered DLT. The MTD will become the RP2D.

Pathologic complete response in the breast at definitive surgery after completion of protocol therapy. The pathologic response to treatment will be assessed by an institutional pathologist at Moffitt Cancer Center. The pathologist will evaluate response by the "Residual Cancer Burden"(RCB) for each participant as described in the online calculator (see RCB link in the More Information section). pCR is defined as no residual invasive carcinoma in the breast and lymph notes at definitive surgery following neoadjuvant therapy

Complete Response (CR) and Partial Response (PR) based upon tumor measurements obtained on physical examination at baseline, after completion of 4 cycles of study therapy. Factors that will be evaluated include: Breast mass(es) - size (longest dimension); Axillary lymph node(s) - size (longest dimension); Skin edema of the breast - present worse, present unchanged, present improved, or absent; Skin erythema of the breast - present worse, present unchanged, present improved, or absent.

Progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.

PFS is defined as the time from study therapy to the first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. This is reported as number of participants who progressed.

Horizon Pharma Ireland, Ltd., Dublin Ireland

H. Lee Moffitt Cancer Center and Research Institute

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 Level 1

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 Level 2

Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 2

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Hyo S. Han, MD

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Combination Therapy

Phase 1: Recommended Phase 2 Dose (RP2D)

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Post Therapy Surgery: Phase 2: Participants will be assessed for surgery following the fourth cycle of study therapy (or earlier if study treatment is cancelled due to unmanageable side effects).

Phase 2: Pathologic Complete Response Rate (pCR)

Complete Response

Partial Response

Stable Disease

Progressive Disease

Phase 2: Clinical Response

Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed

Overall Study

Myotonic Dystrophy Type 1

Pharmaceutical Solutions

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Ado-Trastuzumab Emtansine

Adenosine

Maytansine

Immunotoxins

This study is a phase Ib open label, single arm, adaptive multi-centre trial. Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib (as assigned at registration according to the dose escalation scheme) plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.

Copanlisib is supplied as lyophilized preparation in a 6mL injection vial. The total amount of copanlisib per vial is 60mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Copanlisib will be administered on Days 1 (and 8 and 15 \[according to the dose escalation scheme\]) of each 21-day cycle. Copanlisib will be administered first over 60 minutes followed by the infusion of trastuzumab emtansine.

Copanlisib

Trastuzumab emtansine 3.6mg/kg IV infusion on Day 1 of each 21-day treatment cycle.

Trastuzumab emtansine

Cancer Trials Ireland Dublin 11, Ireland

This study is a Phase 1b open label, single arm, adaptive multi-centre trial of copanlisib in combination with trastuzumab emtansine (T-DM1) in pretreated locally advanced or metastatic HER2-positive breast cancer.

Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib (to the dose escalation scheme) plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.

This study is a phase Ib open label, single arm, adaptive multi-centre trial. Patients with unresectable locally advanced or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, separately or in combination, will be treated with copanlisib plus trastuzumab emtansine 3.6mg/kg IV on day 1 of a 21-day cycle.

3 to 6 patients will be enrolled per dose level. All patients in each level must have completed at least the first cycle of therapy before enrolment in the next dose level begins. Patients not completing the first cycle for a reason other than toxicity will be replaced.

Copanlisib will start at a low level and dose escalations will be performed in cohorts of 3 patients according to a standard 3+3 algorithm.

Dose escalation and determination of maximum tolerated dose (MTD) will be based on occurrences of Dose Limiting Toxicities (DLT).

The first cohort of 3 patients will commence at dose level 1. All patients in each cohort will be observed for one cycle on the specified dose:

* If none of 3 patients at a given dose level experiences a DLT, accrual will continue to the next dose level according to the protocol.
* If 1 of 3 patients experiences a DLT at a given dose level, 3 additional patients will be treated at the same dose. If no additional patient has a DLT in this cohort, accrual will continue to the next dose level according to the protocol.
* If 2 or more patients in 3 or 6 patients treated at a given dose experience a DLT, the dose will be de-escalated to the next lower dose level, which will define the MTD.

If 2 or more patients in 3 or 6 patients treated at the -1 dose level experience DLT, the trial will be stopped.

Primary Objective:

1. To determine the Maximum Tolerated Dose (MTD), for copanlisib in combination with trastuzumab emtansine (T-DM1) in patients with pretreated unresectable locally advanced or metastatic HER2-positive breast cancer.

Secondary Objectives:

1. To evaluate the safety and tolerability of this regimen.
2. To evaluate efficacy measures in patients treated with this regimen.
3. To assess the incidence of cardiotoxicity in patients treated with this regimen.

Exploratory Objectives:

1. To examine for predictive biomarkers in tumour tissue and blood.
2. To examine molecular tumour adaptation to clinical trial therapy.

Copanlisib in Combination With T-DM1 in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

Phase Ib Clinical Trial of Copanlisib in Combination With Trastuzumab Emtansine (T-DM1) in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer "Panthera"

Cancer Trials Ireland

Patritumab deruxtecan

All participants included in the study who answer the eligibility criteria will receive a starting dose of 5.6 mg/kg of U3-1402 every 3 weeks until progression or until unacceptable toxicity

First infusion for 90 minutes and then infusion duration can be progressively decreased to 30 minutes if participant doesn't experience infusion related reactions (IRR)

U3-1402

Barbara Pistilli, Dr

Fernanda Mosele, Dr

Ghada Nachabeh, PM

Barbara Pistili, Dr

This study aims to evaluate the efficacy and safety of U3-1402 in participants with advanced breast cancer (ABC). Participants have to be hormone-receptor positive (HR+) and have to be resistant to endocrine therapy and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors. Participants may have received multiple lines of endocrine therapy with or without targeted therapies and must have received only one line of chemotherapy for ABC.

Moreover, the immune effects, the predictors of resistance and response to treatment, the effect of the chemotherapy on deoxyribonucleic acid (DNA) replication will be assessed and will help identify the subgroups that will mostly benefit from the treatment. The pharmacokinetics of the product and the anti-drug antibody (ADA) will be also evaluated.

A total of 100 participants are planned to be treated in the study. Participants will receive, every three weeks, a dose of U3-1402 equivalent to 5.6 mg/kg of body weight until progression or until unacceptable toxicity.

Tumor evaluation will be performed every six weeks by the mean of a computed tomography for the thorax, abdomen and pelvis (TAP CT-scan) or a magnetic resonance imaging (MRI). Brain and/or bone CT scans will be also performed throughout the study for participants with brain and/or bone metastasis.

The safety of the product will be assessed at each cycle, through complete clinical exams, biological tests, electrocardiograms (ECGs), cardiac echographies (ECHOs) and through the collection of ongoing toxicities or adverse events.

One group of 100 participants receiving U3-1402 (around 170 enrolled with an estimation rate of 70% of screen failures)

Patritumab Deruxtecan (U3-1402) in Unresectable Locally Advanced or Metastatic Breast Cancer

Phase 2, Open Label Study of Patritumab Deruxtecan (U3-1402), an Anti-HER3-Antibody Drug Conjugate (ADC), in Patients With Advanced Breast Cancer, With Biomarker Analyses to Characterize Response to Therapy

Defined as the proportion of participants who achieved a confirmed complete response (CR) or partial response (PR) assessed by investigators

Applicable to participants with either complete response (CR) or partial response (PR) and is defined as the time from the first documented CR or PR until the date of disease progression, or until the date of death. It will be evaluated in the overall population and in subgroups of patients according to their HER3 expression levels

Defined as the time date of the first dose until progression or death from any cause, whichever occurs first. It will be evaluated in the overall population and in subgroups of patients according to their HER3 expression levels

Defined as the presence of at least a PR or CR, or a stable disease (SD) for more than six months under treatment. It will be evaluated in the overall population and in subgroups of patients according to their HER3 expression levels

Defined as the proportion of participants who achieved a confirmed complete response (CR) or partial response (PR) assessed by investigators and will be linked to the levels of HER3 expression

Defined as the time from date of first dose until death.It will be evaluated in the overall population and in subgroups of patients according to their HER3 expression levels

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DESTINY Breast Respond HER2-low Europe	NCT05945732	Unresectable Br... Metastatic Brea... HER2-low Expres...	Trastuzumab der...	18 Years -	Daiichi Sankyo
An Observational Study of Patients Receiving T-DXd for Treatment of HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer	NCT05592483	Breast Cancer	None (Observati...	18 Years - 130 Years	AstraZeneca
ACY-1215 + Nab-paclitaxel in Metastatic Breast Cancer	NCT02632071	Metastatic Brea... Breast Carcinom...	ACY-1215 Nab-paclitaxel	18 Years -	Columbia University
A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer	NCT04872608	Metastatic Brea... Unresectable Br...	Letrozole Palbociclib Onapristone ER	18 Years -	Memorial Sloan Kettering Cancer Center
Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer	NCT03112590	Breast Cancer Breast Cancer, ... Breast Cancer F... HER2-positive B...	Interferon-gamm... Paclitaxel Trastuzumab Pertuzumab Post Therapy Su...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Copanlisib in Combination With T-DM1 in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer	NCT04042051	HER2-positive B... Metastatic Brea... Locally Advance... Unresectable Br...	Copanlisib Trastuzumab emt...	18 Years -	Cancer Trials Ireland
Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer	NCT03112590	Breast Cancer Breast Cancer, ... Breast Cancer F... HER2-positive B...	Interferon-gamm... Paclitaxel Trastuzumab Pertuzumab Post Therapy Su...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Patritumab Deruxtecan (U3-1402) in Unresectable Locally Advanced or Metastatic Breast Cancer	NCT04965766	Metastatic Brea...	U3-1402	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for unresectable breast cancer