Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Atezolizumab

Immunomodulating Agents

Durvalumab

Ibrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Isaiah Dimery

This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.

A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors

A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors

Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.

AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1

Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.

Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1

BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.

Pharmacyclics LLC.

Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.

All subjects who received at least one dose of study treatment.

Phase 1b/2

All participants who received at least one dose of study treatment.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline analysis population includes all patients that received at least one dose of study treatment.

Thorsten Graef

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Phase 1b

Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Phase 2

The Response-evaluable population was participants who received at least 1 dose of treatment (ibrutinib and durvalumab) and provided 1 post-baseline response assessment.

Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.

Phase 1b/2 (Pharmacokinetic Population)

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b and Phase 2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b/2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib

Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)

Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)

Phase 1b: Pharmacodynamics

Participants who enrolled and received at least 1 dose of study treatment.

Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)

All subjects who received at least one dose of ibrutinib and who had at least one evaluable BTK occupancy assay result at Cycle 3 Day 1.

Phase 2: Pharmacodynamics

Period 1

Period 2

Stomach Neoplasms

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Diseases

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

LJM716

Novartis Pharmaceuticals

This primary purpose of this study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) and preferred dosing schedule of LJM716 given by IV infusion in adult patients with squamous cell carcinoma of head and neck, or esophagus, or HER2 overexpressing metastatic breast cancer or gastric cancer

A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

A Phase I Study of LJM716 in Patients With Squamous Cell Carcinoma of Head and Neck, or HER2 Overexpressing Metastatic Breast Cancer or Gastric Cancer

Antibodies

Antibodies, Monoclonal

Trastuzumab

Sacituzumab govitecan

Trastuzumab deruxtecan

Immunoglobulins

Immunoconjugates

Immunologic Factors

Participants will complete the following:

* Baseline visit with assessments.
* CT or MRI scans every 9 weeks for 27 weeks and then every 12 weeks.
* Echocardiogram or MUGA scan every 12 weeks for 24 weeks and then every 16 weeks.
* Cycle 1 through Cycle 2:

  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* Cycle 2:

  * Day 1: Optional tumor biopsy
  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* Cycle 3 through End of Treatment:

  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* End of treatment:

  * Follow up visits every 6 months.

Trop-2-directed antibody-drug conjugate, 180 mg single-dose glass vial, via intravenous infusion per protocol.

Sacituzumab Govitecan

Humanized IgG1 kappa monoclonal antibody, 150mg single-dose vial, via intravenous infusion per protocol.

Recombinant monoclonal antibody, 6 mL vial, via subcutaneous injection per protocol.

Trastuzumab and Hyaluronidase-oysk

Adrienne Waks, MD

Adrienne G Waks, MD

Meredith Faggen, MD

This research study is being done to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer.

The names of the study drugs used in this research study are:

* Sacituzumab govitecan (a type of antibody-drug conjugate)
* Trastuzumab (Herceptin) (a type of monoclonal antibody)
* Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta) (a type of recombinant monoclonal antibody)
* Trastuzumab biosimilar drug

This is an open-label, multi-center, single-arm phase II trial to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer. Participants may receive a biosimilar drug to trastuzumab, which is a nearly identical "copycat" of an original drug that is manufactured by a different company

The U.S. Food and Drug Administration (FDA) has not approved sacituzumab govitecan for Human-epidermal growth receptor 2-positive (HER2+) breast cancer, but it has been approved for triple negative breast cancer and hormone receptor positive but HER2-negative breast cancer.

The U.S. FDA has approved Trastuzumab to be administered as an IV (intravenous) or subcutaneous (injection under the skin) for HER2+ breast cancer.

The research study procedures include screening for eligibility, blood tests, Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans, biopsies, study treatment visits, echocardiograms and/or Multigated Acquisition (MUGA) scans.

It is expected that about 40 people will take part in this research study.

Gilead Sciences Inc. is supporting this research study by providing funding for the trial as well as one of the study drugs, sacituzumab govitecan.

A Single-arm Phase II Trial of SAcituzumab Govitecan and Trastuzumab for HER2+ Metastatic Breast Cancer After Trastuzumab dEruxtEcaN (SATEEN)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.

Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

CBR defined as proportion of participants with Partial Response (PR) + Complete Response (CR) + Stable Disease (SD) ≥6 months per RECIST 1.1

Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.

All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.
A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer	NCT01598077	HER2 + Breast C... HER2 + Breast C... HER2 + Gastric ... Squamous Cell C... Esophageal Squa...	LJM716	18 Years -	Novartis
A Single-arm Phase II Trial of SAcituzumab Govitecan and Trastuzumab for HER2+ Metastatic Breast Cancer After Trastuzumab dEruxtEcaN (SATEEN)	NCT06100874	Her 2 Positive ... Breast Cancer F... Breast Cancer M...	Sacituzumab Gov... Trastuzumab Trastuzumab and...	18 Years -	Dana-Farber Cancer Institute
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.

Spots Global Cancer Trial Database for her2 + breast cancer