Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Cholangiocarcinoma

Breast Neoplasms

Adenocarcinoma

Pancreatic Neoplasms

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Stomach Neoplasms

Sarcoma

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Adenocarcinoma of Lung

Adrenocortical Carcinoma

Biliary Tract Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Biliary Tract Diseases

Endocrine Gland Neoplasms

Endocrine System Diseases

Pancreatic Diseases

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Pancreatic Cancer

Ovarian Cancer

Transitional Cell Carcinoma

Bile Duct Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Biliary Tract Cancer

Germ Cells Tumors

Lung Adenocarcinoma

Testicular Germ Cell Tumor

260 mg once dailly orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

260 mg once daily orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle

RAIN-32

Phase 2, multicenter, single-arm, open-label basket study designed to evaluate the safety and efficacy of milademetan in patients with advanced or metastatic solid tumors refractory or intolerant to standard-of-care therapy that exhibit wild-type (WT) TP53 and MDM2 copy number (CN) ≥ 8 using prespecified biomarker criteria.

Approximately 65 patients will be enrolled to receive milademetan.

Patients will receive the study drug until reaching unequivocal disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1), as determined by the Investigator; experiencing unmanageable toxicity; or until other treatment discontinuation criteria are met. Patients may be treated beyond tumor progression if they are experiencing clinical benefit based on the assessment of the Investigator in discussion with the Medical Monitor.

All patients will be followed for documentation of disease progression and survival information (i.e., date and cause of death). Long-term follow-up will continue every 12 weeks (± 7 days) until the endpoint of death, the patient is lost to follow-up, or for 24 months following the final dose of the study drug, whichever comes first.

Milademetan in Advanced/Metastatic Solid Tumors

A Phase 2 Basket Study of Milademetan in Advanced/Metastatic Solid Tumors (MANTRA-2)

DOR defined as the time from the date of first documentation of CR or PR according to RECIST v1.1 to the date of disease progression or death due to any cause according to Investigator assessment

PFS defined as the time from the date of the first dose of the study drug to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause according to Investigator assessment

GMI defined as the ratio of Time to Progression (TTP) with the nth line of therapy (TTPn; here defined as milademetan) to the most recent prior line of therapy (TTPn-1)

DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks

OS as measured from the date of the first dose of the study drug until the date of death due to any cause

Rain Oncology Inc

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

In the safety run-in, 6 patients will be included milademetan at dose D and fulvestrant 500mg IM at Day1, Day15 of cycle 1, then Day1 of every 28 day-cycle. In case of unacceptable toxicity at the D-dose, a D-1 dose will be investigated, followed by a D-2 dose in case of unacceptable toxicity at D-1 dose.

In the phase II, patients will be treated at the milademetan dose recommended in the safety run-in. Dose reductions will be allowed on subsequent cycles in case of toxicity.

The study treatment, including a combination of milademetan and fulvestrant, is administered into two successive parts: a safety run-in part followed by a phase II part. Once GATA3 mutational status confirmed, patients will continue to receive study drug treatment until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Milademetan

Measure of interest is the mean difference in the change from baseline to different specific visit (each disease radiological assessment, disease progression and/or treatment discontinuation) in total/subscale scores of the 5 Dimension 5 Level (EQ-5D-5L) scale and the EORTC-QLQ-C30 questionnaire

Patient Reported Outcomes (PROs) and Health-Related Quality of Life (HRQOL)

François-Clément Bidard

This is a single arm, multicentric phase II study of milademetan plus fulvestrant in patients with ER+, HER2- ABC harboring GATA3 mutation(s) in the tumor and/or in ctDNA who have progressed on or after prior treatments including a CDK4/6 inhibitor.

Frameshift or truncating GATA3 mutations will be identified by next generation sequencing (NGS) performed on either tissue or circulating DNA. Given the well-known safety profile of fulvestrant and the absence of significant toxicity expected from the association of fulvestrant and milademetan, a safety run-in is planned. During the course of the study, the Steering Committee will specifically review the occurrence of toxicities defined as DLTs in the safety run-in.

This is a single arm, multicentric phase II study designed to evaluate the efficacy and safety of milademetan-fulvestrant combination in patients with ER+ advanced breast cancer. The trial is dedicated to patients experiencing disease progression after one prior line of endocrine therapy, including a prior CDK4/6 inhibitor, but no more than 2 prior lines of endocrine therapy for metastatic disease. No more than 2 prior lines of chemotherapy for metastatic disease is allowed.

The study selection step includes the confirmation of GATA3 mutational status, either with a result already available, or following informed consent form signature, and mutationnal and analysis of FFPE block available as per inclusion criteria.

The study treatment step is divided into two successive parts: a safety run-in part followed by a phase II part.

In the safety run-in, 6 patients will be included at dose D (milademetan 260mg qdx3 every 14 days twice in a 28-day cycle and fulvestrant 500mg IM at Day1, Day15 of cycle 1, then Day1 of every 28 day-cycle. In case of unacceptable toxicity at the D-dose, a D-1 dose will be investigated, followed by a D-2 dose in case of unacceptable toxicity at D-1 dose.

In the phase II, patients will be treated at the milademetan dose recommended in the safety run-in. Dose reductions will be allowed on subsequent cycles in case of toxicity.

Patients will continue to receive study drug treatment until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

This is a single arm, multicentric phase II study designed to evaluate the efficacy and safety of milademetan-fulvestrant combination in patients with ER+ advanced breast cancer. The study treatment step is divided into two successive parts: a safety run-in part followed by a phase II part.

Milademetan and Fulvestrant in GATA3-mutant, ER+HER- Advanced or Metastatic Breast Cancer

Milademetan and Fulvestrant in GATA3-mutant, ER-positive, HER2-negative Advanced or Metastatic Breast Cancer Patients: a Multicenter Phase II Trial

Investigators will share de-identified data sets documents generated under the project will be disseminated in accordance with Institut Curie policies.

The proportion of patients who have achieved either a confirmed complete or partial response, or stable disease for at least 24 weeks after treatment start per RECIST 1.1 based on local investigator assessment.

SAEs (serious adverse events) and AEs (adverse events) according to NCI CTCAE v5.0, by grade and their relationship to milademetan and/or fulvestrant

PFS defined as the time from the date of inclusion until progression per RECIST 1.1 based on local investigator assessment or death due to any cause

ORR defined as the proportion of patients who have a complete response (CR) or partial response (PR) based on local investigator assessment, per RECIST 1.1 among patients with mesurable disease at baseline. If PR/CR is reported, confirmation of response is required; confirmatory assessment should be performed ≥ 4 weeks after response is first documented.

DoR defined as the time from the date of first documented response until date of documented progression or death due to any cause per RECIST 1.1 based on local investigator assessment.

OS defined as the time from inclusion to the date of death due to any cause.

The measure of interest is the mean difference in the change from baseline to different discontinuation in scores of the 5 Dimension 5 Level (EQ-5D-5L) scale

The measure of interest is the mean difference in the change from baseline to different discontinuation in scores of the EORTC-QLQ-C30 questionnaire.

Institut Curie

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Participants receive milademetan alone with different dose schedules.

Participants with advanced melanoma and diffuse large B cell lymphoma (DLBCL) receive milademetan alone with different dose schedules.

DS-3032b will be administered as an oral capsule. It will be supplied in 5, 20, 80, and/or 200 mg capsules individually packaged in desiccant-embedded aluminum blisters.

Milademetan will be administered as a single oral capsule or as a combination of multiple oral capsules containing 5, 20, 80, and/or 200 mg. An alternate combination of 30 and/or 100 mg capsules of milademetan may be utilized.

Global Clinical Leader

This will be a Phase 1, open-label study of milademetan to assess its safety and tolerability, identify a maximum tolerated dose (MTD)/tentative recommended phase 2 dose (RP2D), and assess its pharmacokinetic (PK)/ pharmacodynamic (PDy) properties in participants with advanced solid tumors or lymphomas.

Approximately 5 US sites are planned for Part 1 (Dose Escalation) and Part 2 (Dose Expansion). The same sites are planned to participate for both parts.

A Phase 1 Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas

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/

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Milademetan in Advanced/Metastatic Solid Tumors	NCT05012397	Solid Tumors Head and Neck C... Cholangiocarcin... Sarcoma Lung Adenocarci... Bladder Urothel... Stomach Adenoca... Breast Cancer I... Ovarian Carcino... Cervical Cancer Non Small Cell ... Gastric Cancer Biliary Tract C... Melanoma Pancreas Cancer MDM2 Gene Ampli... Testicular Germ... Adrenocortical ...	RAIN-32	18 Years -	Rain Oncology Inc
Milademetan and Fulvestrant in GATA3-mutant, ER+HER- Advanced or Metastatic Breast Cancer	NCT05932667	Advanced or Met...	Milademetan Patient Reporte...	18 Years -	Institut Curie
Milademetan and Fulvestrant in GATA3-mutant, ER+HER- Advanced or Metastatic Breast Cancer	NCT05932667	Advanced or Met...	Milademetan Patient Reporte...	18 Years -	Institut Curie
A Phase 1 Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas	NCT01877382	Advanced Solid ... Lymphoma	Milademetan Milademetan	18 Years -	Daiichi Sankyo

Spots Global Cancer Trial Database for milademetan

Every month we try and update this database with for milademetan 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 milademetan

Every month we try and update this database with for milademetan 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 milademetan 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.