Breast Cancer Clinical Trials in Philadelphia, PA

This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer. The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in parallel in this study: Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort). Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naive cohort). Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort). Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort). In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). In addition, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment. Read Less

The purpose of this trial is to estimate the recommended dose (RD) of \[177Lu\]Lu-NeoB in combination with ribociclib and fulvestrant in participants with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor-2 (HER2) negative (HER2-) and gastrin releasing peptide receptor (GRPR) positive (GRPR+) advanced breast cancer experiencing early relapse from (neo)adjuvant endocrine therapy or who have progressed on endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease. Read Less

This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment. Read Less

The purpose of this study is to generate evidence on an alternative dosing strategy for CDK4/6 inhibitors to help more patients with Metastatic Breast Cancer (MBC) (age ≥ 65 years) tolerate side effects and stay on treatment longer, to derive the most clinical benefit from these drugs. The primary objective of the CDK Study is to compare time to treatment discontinuation (TTD) on the approved dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider/patient choice endocrine therapy (aromatase inhibitor (AI) or fulvestrant) in patients age 65 or older with HR+/HER2- MBC. The secondary and exploratory objectives will generate evidence needed to personalize treatment decisions by comparing patient-centric secondary outcomes and evaluating baseline factors. Together with their treating physician, participants will choose the CDK4/6 inhibitor (palbociclib or ribociclib) and which endocrine therapy (aromatase inhibitor or fulvestrant) of their choice but will be randomized to either Arm 1 (indicated dosing) or Arm 2 (titrated dosing). Read Less

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDEs based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D). Read Less

Patients with a germline pathogenic variant (GPV) in high-penetrance breast cancer susceptibility genes who are considering risk reducing mastectomy (RRM) often strongly desire to keep their nipple areola complex but inquire as to whether it is safe to do so. Relative to traditional or skin sparing mastectomy (SSM) techniques, nipple sparing mastectomy (NSM) is associated with improved psychosocial and sexual well-being and is significantly better for body image and reducing feelings of disfigurement. Despite this, guidelines have yet to endorse the use of NSM over other RRM techniques, stating that more data and longer follow-up are needed to confirm it as a safe and effective strategy in GPV carriers. As NSM was not routinely adopted in high-risk patient populations undergoing RRM before 2010, there has been little data to inform the long-term oncologic safety of NSM. Well-designed studies have reported low to negligible rates of subsequent breast cancer in BRCA1/2 carriers following NSM, but have been limited by short median follow-up of less than 3 years. The current study is designed to confirm, with longer follow-up, prior findings on the oncologic safety of NSM in unaffected BRCA1/2 carriers. The investigators will also expand data to other high-penetrance GPV carriers, including PALB2, CDH1, PTEN, and TP53, for whom there is little-to-no data on outcomes following RRM. Read Less

This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, and preliminary anti-tumour activity of \[225Ac\]-FPI-1434 (radioimmuno-therapeutic agent) in patients with solid tumours that demonstrate uptake of \[111In\]-FPI-1547 (radioimmuno-imaging agent), and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of \[225Ac\]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of \[111In\]-FPI-1547 (radioimmuno-imaging agent). Read Less

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population. Cohort 1 will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor-positive (ER+), HER2-negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. Cohort 2 will focus on inoperable, locally advanced or metastatic, ER+, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate (ADC; e.g., ado-trastuzumab emtansine or trastuzumab-deruxtecan) or a HER2-targeting tyrosine kinase inhibitor (TKI; e.g., tucatinib, lapatinib, pyrotinib or neratinib). Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy. Read Less

This study evaluates the safety and effectiveness of the da Vinci SP Surgical System compared to Open NSM in Nipple Sparing Mastectomy procedures. Read Less

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors. Read Less

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A\*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation. Read Less

This randomized research trial studies how well serum tumor marker directed disease monitoring works in monitoring patients with hormone receptor positive Her2 negative breast cancer that has spread to other places in the body. Using markers to prompt when scans should be ordered may be as good as the usual approach to monitoring disease. Read Less