Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Antineoplastic Agents, Immunological

All eligible subjects will receive cetuximab treatment only during week 1 of the treatment course and concomitant cetuximab and boost radiotherapy (RT) during week two to week seven of the treatment course

Cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially

* Once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by
* Twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses are separated by at least a 6-hour interval

Cetuximab + concomitant boost radiotherapy

Li Gao

Junliang Cai

Guozhen Xu

Primary objective: to assess the antitumor activity and safety profile of cetuximab when given in combination with radiotherapy (RT) for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in Chinese subjects.

Secondary objective: to assess the pharmacokinetic (PK) profile and immunogenicity of cetuximab in Chinese subjects.

Further objective: to identify for cetuximab potential predictive biomarkers of response and safety.

Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects

Open-label, Single-arm, Multicenter, Phase III Trial to Assess the Antitumor Activity and Safety of Cetuximab When Given in Combination With Radiotherapy for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects

Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD.

Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later).

Merck KGaA, Darmstadt, Germany

An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.

Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Treatment emergent phase, i.e. treatment-emergent adverse events (TEAEs, adverse events which occur or worsen on the first dosing day of trial treatment and until 60 days after the last trial treatment administration (cetuximab or radiotherapy).

Cetuximab: Treatment Emergent Phase

Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Late phase, i.e. adverse events which occur or worsen more than 60 days after the last trial treatment administration (cetuximab or radiotherapy), and before end of trial.

Cetuximab: Late Phase

Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.

Age, Continuous

<65 years

>=65 years

Age, Customized

Sex: Female, Male

Medical Responsible

Intention-to-treat (ITT) population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or RT.

Best Overall Response (BOR)

ITT population included all participants who received at least one dose of the IMP cetuximab or RT.

Progression-Free Survival (PFS)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Mitogens

Naquotinib

Protein Kinase Inhibitors

Enzyme Inhibitors

ASP8273

Medical Director

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

* the safety and tolerability of ASP8273.
* the pharmacokinetics (PK) of ASP8273.
* the antitumor activity of ASP8273.

This study consists of Phase I and Phase II.

The objectives of Phase I are to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

* safety and tolerability of ASP8273.
* the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ASP8273 based on the dose limiting toxicity (DLT) profile.
* pharmacokinetics (PK) of ASP8273.
* antitumor activity of ASP8273.

The objectives of Phase II are to determine the following at the RP2D of ASP8273 in patients with NSCLC harboring EGFR mutation.

* efficacy of ASP8273
* safety of ASP8273
* PK of ASP8273

An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

An Open-label Study of the Oral Administration of ASP8273 in Patients With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Mutations

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE ver 4.0 - JCOG)

The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated

An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product

Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation

Vital signs to be measured includes blood pressure, pulse rate and temperature

The overall response rate is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated

The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.

Astellas Pharma Inc

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Anti-Infective Agents

Peposertib

Trichostatin A

Participants received MSC2490484A capsules 100 milligram (mg) orally, once daily (QD) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 200 mg orally, QD from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 150 mg orally, twice daily (BID) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 200 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 300 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 400 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules 400 mg recommended Phase II dose (RP2D) orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

Participants received MSC2490484A capsules at escalated dose from 100 mg to 400 mg orally from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.

MSC2490484A (M3814)

MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). This is a first-in-man Phase I study, which means that it is the first time the study drug is being used in humans. The main purpose is to determine the highest dose that does not cause unacceptable side effects. The second is to determine the appropriate dose to use in future research for subjects with cancer. Othergoals of the study are to learn about the drug's safety and side effects, how it affects the tumor, and how the body processes the drug.

This is a Phase I, first-in-human, open-label, dose escalation, and dose expansion trial designed to explore the safety, tolerability, PK and PD profiles, and clinical activity of MSC2490484A administered daily as a single agent to subjects with advanced solid tumors or CLL likely to have alterations in DNA repair mechanisms.

Dose Escalation : Subjects will receive MSC2490484A continuously at the starting dose of 100 mg once daily. Sequential treatment cohorts will receive ascending doses of MSC2490484A once daily or twice daily (if determined to be appropriate by the Safety Monitoring Committee \[SMC\]) following a standard "3+3" design. The SMC will make dose escalation decisions based on review of available safety, tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) data. Once the maximum tolerated dose (MTD) has been established, an Recommended Phase II Dose (RP2D) will be defined by the SMC, either at the MTD level or another dose level, depending on the available data on safety, efficacy, PK, and PD observed in the trial. The SMC may decide to stop dose escalation at any time during the trial.

Up to 12 subjects will be enrolled at the RP2D/Optimal biologic dose (OBD) to confirm safety and tolerability and explore the PK and PD profile of MSC2490484A.

Expansion cohorts: Once subjects have been evaluated at the RP2D, additional subjects will be enrolled into 2 or more expansion cohorts (20 evaluable subjects per expansion cohort) to evaluate clinical efficacy in tumors likely to have alterations in the DNA repair mechanism (eg, CLL and other tumor types). Subjects are evaluable for efficacy if they have received at least 1 dose of study drug and have radiographic baseline. Subjects who are not evaluable for efficacy will be replaced.

Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia

A Multicenter, Open-Label, Dose-Escalating Phase I Trial of the DNA-PK Inhibitor MSC2490484A in Subjects With Advanced Solid Tumors or Chronic Lymphocytic Leukemia

Carboplatin

Carboplatin starting dose AUC of 4, administered by vein over 60 minutes, Day 1 of 3 Week Cycle. TAS-106 starting dose 2.0 mg/m\^2 by vein over 24 hours, Day 1 of 3 Week Cycle.

Starting dose 2.0 mg/m\^2 by vein over 24 hours, Day 1 of 3 Week Cycle.

TAS-106

Starting dose AUC of 4, administered by vein over 60 minutes, Day 1 of 3 Week Cycle.

Aung Naing, MD

The goal of this clinical research study is to find the highest safe dose of the combination of TAS-106 and carboplatin that can be given to patients with advanced cancer or cancer that has spread.

Objectives:

Primary Objectives:

To determine the maximum tolerated dose (MTD) of the combination of TAS-106 and carboplatin administered by intravenous infusion every 3 weeks.

To perform Pharmacokinetic (PK) analysis of TAS-106 and carboplatin

Secondary objectives:

To assess the antitumor activity of TAS-106 combined with carboplatin

To investigate the relationship between selected biomarkers and efficacy and safety outcomes.

The Study Drugs:

TAS-106 and carboplatin are designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Study Drug Dose Level:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of the study drug combination that is based on when you joined this study. Up to 6 dose levels of the study drug combination will be tested. Three (3) participants will be enrolled at each dose level. If no intolerable side effects occur in the first group of 3 people, the next 3 people enrolled in the study will receive the same dose of carboplatin and a higher dose of TAS-106. If this second group has no intolerable side effects, the next 3 people will receive a higher dose of carboplatin while receiving the same dose of TAS-106 as the second group. This will continue until the highest safe dose combination is found.

Study Drug Administration:

A "cycle" in this study is 3 weeks long. On Day 1 of each cycle, you will receive carboplatin by vein over 60 minutes, followed by TAS-106 by vein over 24 hours.

Study Visits:

On Day 1 of each cycle (+/- 1 day), you will come to the clinic to have the following procedures performed:

* You will have a complete physical exam, including measurement of vital signs and weight.
* You will have a neurological exam.
* You will be asked about any drugs you have taken recently and any side effects you may have experienced. The study doctor may give you drugs to lessen any possible side effects.
* You will have a performance status evaluation.
* Blood (about 3 teaspoons) and urine will be collected for routine tests.

On Day 1 of Weeks 2 and 3 of each cycle (+/- 3 days), blood (about 3 teaspoons) will be drawn for routine tests. If your blood cell counts (white blood cells, red blood cells, and/or platelets) drop to a low level, you may need to have these routine tests repeated more often than once a week.

At the end of every 2 cycles (+/- 1 week), you will have CT scans, MRI scans, and/or x-rays to check the status of the disease.

You must stay in the Houston area during Cycle 1. During that time, all blood tests and other study tests and procedures must be done at MD Anderson. Starting in Cycle 2, if you prefer, you may have the blood tests at Weeks 2 and 3 of each cycle performed at a medical laboratory that is close to your home. If you need to have the additional blood cell count testing performed as well, those blood tests can also be done close to home. All other study tests and procedures must be done at M. D. Anderson.

Length of Study Participation:

You may continue to stay on the study drugs for as long as you are benefiting. If the cancer gets worse or you experience intolerable side effects, you will be taken off study. If you experience side effects that are severe but not intolerable, however, your doctor may decide that it is necessary to delay your next dose of the study drug combination and/or lower the dose.

End-of-Study Visit:

When you go off study for any reason, you will have an end-of-study visit with all of the same tests performed as at your other study visits. You will also have an ECG.

This is an investigational study. Carboplatin is FDA approved and commercially available for other uses. TAS-106 is not FDA approved or commercially available. The combination of carboplatin and TAS-106 is not FDA approved or commercially available. At this time, the combination is being used in research only.

Up to 55 patients will take part in this study. All will be enrolled at MD Anderson.

Phase I Study of TAS-106 in Combo With Carboplatin

Phase I Dose Escalating Study Of Tas-106 In Combination With Carboplatin In Patients With Solid Tumors

Taiho Pharmaceutical Co., Ltd.

M.D. Anderson Cancer Center

Nervous System Diseases

Recurrence

Glioma

Pinealoma

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Pineocytoma

Neuroepithelioma

Hypoglycemic Agents

Antibodies

Antibodies, Monoclonal

Insulin

Insulin, Globin Zinc

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

IMC-A12

Dennis D Hickstein, M.D.

Background:

- IMC-A12 is an experimental substance designed to inhibit a protein called Type I Insulin-Like Growth Factor Receptor (IGF-1R), which can be found on cancer cells and can promote cancer growth. Temsirolimus is a drug that the U.S. Food and Drug Administration has approved to treat advanced renal cell carcinoma in adults. Researchers do not know if the combination of IMC-A12 and temsirolimus will work in children, but want to determine whether these two drugs may be an effective treatment for recurrent tumors.

Objectives:

* To determine the safety and effectiveness of IMC-A12 and temsirolimus in treating children and adolescents with solid tumors.
* To determine possible side effects of the combination of IMC-A12 and temsirolimus.

Eligibility:

- Children and adolescents between 12 months and 21 years of age who have solid tumors that have not responded to or have relapsed after standard treatment.

Design:

* Participants will be screened with a medical history, physical examination, and imaging studies.
* Participants will receive IMC-A12 and temsirolimus in 28-day cycles of treatment. IMC-A12 will be given as an infusion over 1 hour, once a week, for 4 weeks. Temsirolimus will also be given after IMC-A12 over 30 minutes, once a week, for 4 weeks.
* Participants may continue to receive IMC-A12 and temsirolimus for up to 2 years unless serious side effects develop or the treatment stops being effective.
* Participants will have additional physical exams, blood and urine tests, and imaging studies regularly during each treatment cycle.
* Participants will be followed at regular intervals after the end of the study to collect tumor response and progression data....

Background

* IMC-A12 is a fully recombinant IgG1monoclonal antibody to the insulin-like growth factor receptor (IGFR). It acts as an antagonist of IGF-1 and IGF-2 ligand binding and blocks ligand binding to IGF-1R and inhibits downstream signaling of the two major insulin-like growth factor pathways: MAPK and PI3K/AKT.
* Temsirolimus is a small molecule inhibitor of mTOR, which like rapamycin and everolimus forms a complex with FK506-binding protein (FKBP)12 and mTOR, inhibiting mTOR and leading to anti-proliferative effects, including G1 phase cell cycle arrest and apoptosis.
* Inhibition of mTOR signaling leads to upregulation of IGF-1R signaling which leads to activation of the PI3K/AKT/mTOR pathway. Pediatric pre-clinical models have demonstrated synergistic anti-tumor effects combining IGF-1R antibodies and mTOR inhibitors.

Objectives

* To determine the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) administered as an intravenous infusion once weekly in combination with temsirolimus administered intravenously once weekly to children with refractory solid tumors.
* To define the toxicities of the combination regimen and characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in this patient population.
* Secondary objectives include defining in a preliminary fashion antitumor activity, assessing biologic activity of IMC-A12 and temsirolimus and assessing the incidence of IGFR expression and mTOR pathway activation in recurrent or refractory solid tumors of childhood.

Eligibility

* Patients \> 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas or pineal tumors and elevations of serum or CSF alpha-fetoprotein or beta-HCG) of measureable or evaluable relapsed or refractory solid tumors. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival.
* Must have fully recovered from acute toxic effects from all prior therapy, which has been completed within the specified prior time frame.
* Have adequate organ function as determined by laboratory evaluation including normal random or fasting blood glucose within the upper normal limits for age and grade \< 2 serum cholesterol and triglyceride levels.
* Subjects with uncontrolled infection, known type I or type II diabetes mellitus, known bone marrow involvement or who have received prior monoclonal antibody therapy targeting IGF-1R or temsirolimus are not eligible.

Design

* This is a phase I study of IMC-A12 administered every 7 days as a 1-hour intravenous infusion at a starting dose of 6 mg/kg. Temsirolimus will be administered intravenously over 30 minutes immediately after IMC-A12 on a once weekly schedule, at a starting dose of 15 mg/m(2).
* One cycle of therapy is considered to be 28 days. Therapy may continue for up to 2 years in the absence of progressive disease or unacceptable toxicity.
* All patients will have required trough blood samples for pharmacokinetic analysis of IMC-A12 and temsirolimus and immunogenicity studies collected at the same time as select routine safety labs. Optional participation in additional pharmacokinetic studies and correlative biology studies will be offered.

A Phase I Study of IMC-A12 in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors

A Phase I Study of IMC-A12 (Anti-Insulin-like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors

National Cancer Institute (NCI)

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.

MEDI5752

This is a Phase 1, open-label study evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of MEDI5752 in Japanese patients with advanced solid solid tumors.

\<Objectives\>

Primary Objective:

To evaluate the safety and tolerability of MEDI5752 in Japanese subjects with advanced solid tumors.

Secondary Objective:

To assess the anti-tumor activity and efficacy of MEDI5752. To describe the pharmacokinetics of MEDI5752.

Exploratory Objective:

To conduct exploratory research into factors that may be predictive of response or may influence the progression of cancer and/or response (efficacy) to MEDI5752.

Eligible patients will be administered as a single dose at each Cycle Day1. Each cycle from Cycle 1 has a duration of 21 days.

A minimum of 3 and a maximum of 9 evaluable patients will be enrolled in each cohort.

MEDI5752 in Japanese Patients With Advanced Solid Tumors.

A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Japanese Subjects With Advanced Solid Tumors

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v5.0.

The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v5.0.

The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.

The primary endpoint is as assessed as the number of subjects experiencing changes in laboratory parameters from baseline.

The primary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.

The primary endpoint is as assessed by the the number of subjects experiencing clinically significant changes in ECG parameters from baseline.

The endpoints for assessment of antitumor activity is defined by using ORR, PFS, BOR,DCR, DoR and TTR according to RECIST v1.1.

The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. (e.g., Maximum plasma concentration\[Cmax\]）

The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)

The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects	NCT01012258	Squamous Cell C...	Cetuximab + con...	18 Years -	Merck KGaA, Darmstadt, Germany
An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations	NCT02192697	Non-small Cell ...	ASP8273	20 Years -	Astellas Pharma Inc
Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia	NCT02316197	Advanced Solid ... Chronic Lymphoc...	MSC2490484A (M3...	18 Years -	Merck KGaA, Darmstadt, Germany
Phase I Study of TAS-106 in Combo With Carboplatin	NCT00752011	Cancer Solid Tumors	TAS-106 Carboplatin	18 Years -	M.D. Anderson Cancer Center
Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects	NCT01012258	Squamous Cell C...	Cetuximab + con...	18 Years -	Merck KGaA, Darmstadt, Germany
Phase I Study of TAS-106 in Combo With Carboplatin	NCT00752011	Cancer Solid Tumors	TAS-106 Carboplatin	18 Years -	M.D. Anderson Cancer Center
A Phase I Study of IMC-A12 in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors	NCT01182883	Brain Stem Neop... Glioma Pinealoma	IMC-A12 Temsirolimus	1 Year - 21 Years	National Institutes of Health Clinical Center (CC)
MEDI5752 in Japanese Patients With Advanced Solid Tumors.	NCT05685472	Advanced Solid ...	MEDI5752	18 Years - 120 Years	AstraZeneca

Spots Global Cancer Trial Database for antitumor activity