Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Microsatellite Instability

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Genomic Instability

Turcot Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

In the pembrolizumab + RT arm, pembrolizumab will be started on study within 7 days (+/- 7 days) of start of RT.

Pembrolizumab will be given as standard of care in both arms

anti-PD-1 therapy alone Pembrolizumab will be given as standard of care in both arms

RT and Anti-PD-1

Anti-PD-1

To determine if the out-of-field ORR is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. Determine the rates of in-field tumor control, disease control (stable disease, partial response, complete response), durability of disease response, progression-free survival, overall survival, and to assess quality of life and toxicity. Determine the chronology and profile of the radiation-associated immune response.

This is a randomized phase II study with a primary objective to compare the objective response rate (ORR) for anti-PD-1 therapy alone versus anti-PD-1 therapy and limited metastatic site radiation, in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic solid tumors. The anti-PD-1 agent, pembrolizumab, received recent FDA accelerated approval for the use in patients with metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment or without satisfactory alternative treatment options. FDA approval for pembrolizumab was based on the results of five multi-cohort, multi-center, single-arm trials, which together showed an ORR of 39.6% among 149 patients with MSI-H/dMMR cancers. Importantly, there is mounting preclinical and clinic evidence supporting the safety and efficacy of combining radiation therapy with systemic immunotherapy, although no prospective comparative data, to the best of our knowledge. In this study, the investigators will focus on patients with MSI-H/dMMR tumors, given their baseline responsiveness to immune checkpoint inhibition, and test the hypothesis that ORR will be improved with radiation and anti-PD-1 therapy compared to anti-PD-1 therapy alone, through a randomized phase II trial design.

In an effort to minimize bias, the study will utilize a randomization. The randomization list will be generated by the study biostatistician and provided only to the study personnel who will be responsible for assigning each subject to a cohort of the study.

Anti-PD-1 +/- RT for MSI-H Solid Tumors

A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors

• Out-of-field objective response rate (ORR: CR+PR) according to RECIST 1.1 assessment

In-field tumor control and disease control will be defined as SD, PR, or CR, of the target lesion, by RECIST 1.1 criteria

The University of Colorado School of Medicine Human Immune Monitoring Shared Resource (HIMSR) will quantify peripheral CD8, CD4, and regulatory T cell populations and characterize the relative functional state of these cells using activation markers (CD45RO, ICOS, and CD25) and inhibitory markers (TIM-3, CTLA-4, LAG-3, and PD-1). The HIMSR will also characterize peripheral dendritic cells (pDCs, CD1c+, and CD141+ subsets), monocytes (classical and non-classical subsets), myeloid-derived suppressor cells (MDSCs, granulocytic and monocytic subsets), and expression of activation (CD80 and HLA-DR) and inhibitory molecules (PDL1) on these cells. Further, cytokine production by NK cells, B cells, T cells, and monocytes will be measured by flow cytometry after brief ex-vivo stimulation. The HIMSR will also perform a protein multiplex array of 40 potential biomarkers in plasma.

In patients that achieve an objective response to pembrolizumab +/- RT, durability of response will be measured from the initiation of pembrolizumab until PD.

Progression-free survival will be measured from the date of initiation of pembrolizumab to the time of tumor progression or death from any cause for one year.

Overall survival will be measured from the date of initiation of pembrolizumab to the time of death from any cause for one year.

Quality of life questionnaire, 28 questions rating experience from 1 to 4 (4 being "very much", 1 being "not at all") and two questions rating overall health and quality of life on a scale from 1 to 7 (7 being excellent)

National Cancer Institute (NCI)

Cancer League of Colorado

University of Colorado, Denver

Adenocarcinoma

Stomach Neoplasms

Neoplasm Metastasis

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Trastuzumab

Trastuzumab deruxtecan

Antibodies

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer will be treated with trastuzumab deruxtecan by intravenous (IV) infusion every 3 weeks, until progression of disease or withdrawal from treatment for other reasons.

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion

Global Clinical Leader

This study will find out if trastuzumab deruxtecan is safe and works for participants with gastric or gastroesophageal junction cancer.

They must have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer:

* that cannot be removed surgically
* that has moved to other parts of the body
* that got worse during or after treatment that included trastuzumab

The study will enroll about 80 participants. Sites will be in North America and the European Union.

DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)

A Phase 2, Open-label, Single-arm Trial of Trastuzumab Deruxtecan (DS 8201a) in HER2-positive, Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-containing Regimen (DESTINY-Gastric02)

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported.

Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported.

Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.

Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR based on independent central review.

AstraZeneca

Daiichi Sankyo

A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.

Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer received an intravenous (IV) infusion 6.4 mg/kg dose of trastuzumab deruxtecan every 3 weeks, until progression of disease or withdrawal from treatment for other reasons.

Trastuzumab Deruxtecan

Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer treated with trastuzumab deruxtecan by intravenous (IV) infusion every 3 weeks, until progression of disease or withdrawal from treatment for other reasons.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Belgium

United States

Italy

United Kingdom

Spain

Region of Enrollment

Contact for Clinical Trial Information

Objective response rate was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.

Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Objective response rate was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.

Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.

Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Progression-free survival (PFS) was assessed in the Full Analysis Set data at cut-off date of 08 Nov 2021

Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.

Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.

Duration of Response (DOR) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.

Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma

Duration of Response (DOR) was assessed in the Full Analysis Set at data cut-off date of 08 Nov 2021.

Overall Study

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Neuroendocrine Tumor

Neuroepithelioma

Gastrointestinal Agents

Octreotide

Antineoplastic Agents, Hormonal

The patients with unresectable or metastatic GEP or esophageal NEC who got CR/PR/SD after chemotherapy with IP or EP regimen qualified with the inclusion criteria are enrolled. All the patients enrolled in our study will be randomly assigned to receive octreotide LAR (group A) as maintenance treatment or follow up (group B) to disease progression.

Octreotide lar

Lin Shen, Prof

Jie Li, Prof

This is phase II study on the efficacy of octreotide lar as maintenance treatment after first-line chemotherapy for patients with unresectable or metastatic gastro-entero-pancreatic or esophageal neuroendocrine carcinomas.

This is a prospective, randomized, open label study on the efficacy of octreotide lar as maintenance treatment after first-line chemotherapy for patients with unresectable or metastatic gastro-entero-pancreatic or esophageal neuroendocrine carcinomas.The patients with unresectable or metastatic GEP or esophageal NEC who got CR/PR/SD after chemotherapy with IP or EP regimen qualified with the inclusion criteria are enrolled. All the patients enrolled in our study will be randomly assigned to receive octreotide LAR (group A) as maintenance treatment or follow up (group B) to disease progression. Treatment will be discontinued on withdrawal of patient consent, disease progression, unacceptable toxicity, a treatment delay of \>2 weeks, or major protocol violations, after which patients were followed up every 3 months for a minimum of 12 months.

Octreotide LAR as Maintenance Treatment for Patients With NEC

Randomized Phase II Study of Octreotide LAR as Maintenance Treatment After First-line Chemotherapy for Patients With Unresectable or Metastatic Gastro-entero-pancreatic or Esophageal Neuroendocrine Carcinomas

Peking University

GI Oncology Department

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Pharmaceutical Solutions

Gemcitabine

Capecitabine

Paclitaxel

Albumin-Bound Paclitaxel

Mitogens

Camptothecin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Topoisomerase I Inhibitors

Enzyme Inhibitors

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:

* Capecitabine
* Eribulin
* Gemcitabine
* Paclitaxel
* Nab-paclitaxel

DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously

Trastuzumab deruxtecan (DS-8201a)

Administered according to label, as one option for Physician's Choice (determined before randomization)

Eribulin

Nab-paclitaxel

This study will compare DS-8201a to physician choice standard treatment.

Participants must have HER2-low breast cancer that has been treated before.

Participants' cancer:

* Cannot be removed by an operation
* Has spread to other parts of the body

This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.

Parallel model, randomized at a 2:1 ratio

Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.

Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.

Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Daiichi Sankyo Co., Ltd.

All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.

Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.

Trastuzumab Deruxtecan (T-DXd)

Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.

Physician's Choice

Total

White

Black or African American

Asian

Native Hawaiian or other Pacific Islander

Other

Missing

Race/Ethnicity, Customized

Baseline characteristics were assessed in the Full Analysis Set. The Full Analysis Set included all participants randomized into the study, including those who did not receive a dose of study treatment. Participants were analyzed according to the treatments and strata assigned at randomization.

Progression-free survival (PFS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer

Progression-free survival (PFS) was assessed in the Full Analysis Set.

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status

Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer

Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)

Overall survival (OS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer

Overall survival events (deaths) were analyzed in the Full Analysis Set (defined as all randomized participants).

Number of Overall Survival Events (Deaths)

Overall survival (OS) was assessed in the Full Analysis Set (defined as all randomized participants).

Overall Survival (OS) in All Patients

BICR: Complete response

BICR: Partial response

BICR: Stable disease

BICR: Progressive disease

BICR: Not evaluable

Investigator: Complete response

Investigator: Partial response

Investigator: Stable disease

Investigator: Progressive disease

Investigator: Not evaluable

BICR: Confirmed Objective response rate

Investigator: Confirmed Objective response rate

Best overall response and confirmed objective response rate were assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anti-PD-1 +/- RT for MSI-H Solid Tumors	NCT04001101	Microsatellite ... Mismatch Repair... Colorectal Canc...	RT and Anti-PD-... Anti-PD-1	18 Years - 100 Years	University of Colorado, Denver
DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)	NCT04014075	Adenocarcinoma ... Adenocarcinoma ...	Trastuzumab der...	18 Years -	Daiichi Sankyo
Octreotide LAR as Maintenance Treatment for Patients With NEC	NCT02409849	Gastro-entero-p... Esophageal Neur...	Octreotide lar	-	Peking University
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]	NCT03734029	Breast Cancer	Trastuzumab der... Capecitabine Eribulin Gemcitabine Paclitaxel Nab-paclitaxel	18 Years -	Daiichi Sankyo
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]	NCT03734029	Breast Cancer	Trastuzumab der... Capecitabine Eribulin Gemcitabine Paclitaxel Nab-paclitaxel	18 Years -	Daiichi Sankyo
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer	NCT03505710	Non-Small Cell ...	Trastuzumab der...	18 Years -	Daiichi Sankyo
Octreotide LAR as Maintenance Treatment for Patients With NEC	NCT02409849	Gastro-entero-p... Esophageal Neur...	Octreotide lar	-	Peking University

Spots Global Cancer Trial Database for unresectable or metastatic