Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Recurrence

Prostatic Neoplasms

Neoplasm Metastasis

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplastic Processes

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Immunomodulating Agents

Durvalumab

Antineoplastic Agents, Immunological

Radiation (SBRT) + Immunotherapy treatment (Durvalumab)

64 patients will be enrolled in this arm

Durvalumab, will be started one month prior to SBRT and then given for a total of 12 months.

Patient will receive one injection per months (1500 mg/cycle)

SBRT will be started one month after Durvalumab and patients will receive 3 fractions of radiation

Radiation (SBRT)

32 patients will be enrolled in this arm

Patients will receive only 3 fractions of radiation

Durvalumab, MEDI4736, is a immunotherapy,

SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy

SBRT + Durvalumab

SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy

SBRT

STEPHANE SUPIOT

As in other solid tumours, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis compared with patients with extensive metastatic disease.

Survival of patients with three or fewer metastases was superior compared with patients with more than three lesions.

The introduction of novel imaging modalities such as Fluorocholine (FCH), Fuciclovine or Ga-PSMA PET CT has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy with radiotherapy (RT).

Based on several studies, SBRT is now considered as a strongly validated option in oligometastatic prostate cancer.

It is increasingly understood that cancers are recognized by the immune system, and, under some circumstances, the immune system may control or even eliminate tumors.

Programmed death-ligand 1 (PD-L1) is transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events.

PD-L1 is expressed in a broad range of cancers. Based on these findings, an anti-PD-L1 antibody could be used therapeutically to enhance antitumor immune responses in patients with cancer.

Experimental data from multiple cancer models have provided cumulative evidence of an interaction of ionizing radiation with the systemic antitumor immunity and this has created several opportunities in the field.

The oligometastatic setting appears to be the most relevant clinical situation to evaluate the immune response generated by radiotherapy and immune modifiers in patients with an intact immune system. The hypothesize is that Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this randomized 2:1 phase II trial of Stereotactic Body Radiation Therapy with or without durvalumab in oligometastatic hormone sensitive prostate cancer patients, Durvalumab will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT and then given adjuvantly for a total of 12 months.

Prostate Cancer With OligometaSTatic Relapse: Combining Stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736)

A Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) With or Without Durvalumab (MEDI4736) in Oligometastatic Recurrent Hormone Sensitive Prostate Cancer Patients

The primary outcome will be progression-free survival, defined as the time from randomization until a biochemical-clinical failure

Health-related quality of life will be evaluated using EORTC QLQ-PR25 instruments.Total score is reported

Health-related quality of life will be evaluated using self-administered EORTC QLQ-C30 questionnaire. Total score is reported

ADT will be started in both arms at time of polymetastatic disease, local progression of metastases or symptoms.

AstraZeneca

Institut Cancerologie de l'Ouest

Analgesics

Mitoxantrone

Docetaxel

Satraplatin

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Preoperative chemotherapy using Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.

Procedure: radical prostatectomy surgery.

No neoadjuvant chemotherapy using CDMS will be done for patients who are diagnosed with localized prostate cancer but subject to direct surgery to radically remove the primary tumor.

As preoperative neoadjuvant chemotherapy, drugss including Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) will be administered as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.

Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin

Yu Sun, Ph.D

Weijun Ma, Ph.D

Jiannan Chen, Ph.D

Qilai Long, Ph.D

Current agents administered in therapeutic regimens of prostate cancer employ different mechanisms to eliminate neoplastic cells by inducing substantial apoptosis and causing tumor regression. Treatment with neoadjuvant chemotherapy before radical prostatectomy may better control the tumor before it has the chance to convert into the disease of castration-resistant prostate cancer (CRPC), which is finally refractory to most modalities of clinical intervention with a clinically lethal nature.

Prostate cancer is the development of neoplasia in the prostate, a major gland in the male reproductive system. While most prostate cancers grow slowly, some can develop relatively quickly and aggressively. In a later stage of the disease, cancer cells may disseminate from the prostate to other organs of the body, particularly the bone, lung, brain and lymph node. Prostate cancer initially cause no symptoms, but in an advanced stage it can cause difficulty in urinating, blood in the urine, or pain in the pelvis. A non-malignant or precursor form of prostate cancer known as benign prostatic hyperplasia may produce similar symptoms, although it is essentially not invasive.

Many prostate cancer patients can be safely followed with active surveillance or watchful actions. However, the major forms of clinical treatments include a combination of surgery, radiation, hormone therapy or chemotherapy. If it only occurs inside the prostate, the disease is generally curable. However, when cancer cells have spread to the bones, cytotoxic or harsh therapies are necessary. Outcomes depend on a person's age and other health conditions as well as how aggressive and extensive the cancer is. Most people with prostate cancer do not end up dying from the disease, and the 5-year survival rate in the United States is approximately 99%. To date, it is the 2nd most common type of malignancy and the 5th leading cause of cancer-related death in men. In 2012 it affected 1.1 million men and claimed 307,000 deaths. Prostate cancer occur more frequently in the western countries or developed world, but incidence rates have been continuously arising in the developing countries. Clinical detection increased significantly in the 1980s and 1990s in the global range due to development of the gold standard--PSA testing. Studies of males who died from unrelated causes have found prostate cancer in 30% to 70% of those over the age of 60.

Most hormone-naive prostate cancers become resistant to treatments after 1-3 years and resume growth despite hormone therapy, a condition termed as "hormone-refractory prostate cancer" (HRPC) or "castration-resistant prostate cancer (CRPC)". The most prevalent chemotherapeutic agent docetaxel (Taxotere) has been used as a standardized modality for CRPC and provides a median survival benefit of 2-3 months. A second-line chemotherapy involves cabazitaxel. Although combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC, these agents are usually used after the occurrence of CRPC, not before. Thus, whether or not these patients should receive chemotherapy prior to development of CRPC, and whether this approach can prevent the aggressive progression of the disease to a treatment refractory status, remain largely open but intriguing questions.

In this study, investigators performed a Phase I, single agent exploration, multicenter clinical trial to establish the treatment efficacy of several chemotherapeutic agents in patients with high risk localized prostate cancer who have developed the primary cancer in prostate. Up to 5 cohorts have been enrolled to determine the effectiveness and safety of single therapeutic strategy. Besides the five-year disease-free survival, overall survival and five-year metastasis-free survival post treatment, investigators also take into account the anticancer agent-induced tumor stroma damage extent, which may provide further evidence to support the treatment efficacy and assess the potential influence of a damaged tumor microenvironment on disease progression or regression in clinical settings.

Chemotherapy (single agent of CDMS) will be performed 45 days before surgery for patients who are diagnosed with prostate cancer without distant metastasis. The chemotherapy using CDMS will done for 4 cycles within 30 days after first diagnosis of prostate cancer.

Both the participants and care providers will be blind to the agents, but the investigators will be aware of and keep track of the whole regime and agents.

All participant patients should be male, adult.

A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis

A Phase I Study of Neoadjuvant Chemotherapy Involving Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Followed by Surgery for Patients With High Risk Localized Prostate Cancer

Investigators are happy to make individual participant data (IPD) available to other researchers upon request, as long as the data are not confidential and not restrained by the ethics policy.

There is no disease-associated progression during the 5 years post treatment (chemotherapy plus surgery).

The overall survival status and distant metastasis-free survival status during the 5 years post treatment (chemotherapy plus surgery).

Fudan University

Qilu Hospital of Shandong University

Shanghai Jiao Tong University School of Medicine

Professor

Psychotropic Drugs

Hypoglycemic Agents

Cardiotonic Agents

Bupropion

Repaglinide

Antidepressive Agents

Dopamine

Dopamine Uptake Inhibitors

Dopamine Agents

Neurotransmitter Agents

Cytochrome P-450 Enzyme Inhibitors

* Experimental: Repaglinide, Bupropion and SHR3680
* Repaglinide and Bupropion QD on Day 1 and Day 21, SHR3680 240 mg once daily (QD) from Study Day 6 - 26

Single dose of oral administration of Repaglinide and Bupropion, Multiple dose of oral of SHR3680

Repaglinide, Bupropion and SHR3680

Yuya Wang, Ph.D

shijuan kuang, Master

Weiqing Han, Ph.D

The DDI study had been designed to investigate the effect of SHR3680 on the pharmacokinetics of Repaglinide and Bupropion

Drug-drug Interaction of SHR3680 With Repaglinide and Bupropion

A Single-center, Open-label, Fixed-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of SHR3680 With Repaglinide (CYP2C8 Substrates) and Bupropion (CYP2B6 Substrates) in Prostate Cancer Patients

Summary of Pharmacokinetic parameters Maximum Plasma concentration (Cmax) for Repaglinide and Bupropion

Summary of Pharmacokinetic parameters Area Under the Plasma Concentration-time Curve form 0 to any time before the last quantifiable concentration(AUC0-t)for Repaglinide and Bupropion

Jiangsu HengRui Medicine Co., Ltd.

Disease Progression

Subjects will be administered with 250 milligram (mg), 500 mg, 1000 mg or 1500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of week 6 were continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject is no longer benefitted from the treatment as per Investigator's discretion.

EMD 525797

Wolfgang Uhl, Dr, Dipl. Chem., Physician

This study is intended to test an experimental new drug called, EMD 525797 (Study Drug). This drug is not yet approved for sale and has only been tested in a small number of people to date (prior to this study starting another research study was carried out involving 37 healthy volunteers receiving the Study Drug). Until more is known about this Study Drug, it can only be used in research studies.

This research study is planned to answer important questions about how the Study Drug is tolerated and how it may work in patients with prostate cancer with bone metastases.

This is a small study which is expected to include 24 patients, and will be conducted in approximately 3 hospitals in Germany and 1 hospital in Brussels, Belgium. The study will last until the last patient has had their last study visit which is expected to be about 18 months in total.

A Study to Determine the Safety, Tolerability, Pharmacokinetics and Dynamic Effects of Different Doses of the Study Drug EMD 525797 in Prostate Cancer

Phase I, Open-label Study to Investigate Safety, Tolerability, PK, and PD of EMD 525797 After Single and Repeated Dosing at Different Dose Levels in Subjects With Hormone-resistant Prostate Cancer With Bone Mets and Progressive Disease Following Prior CTX

DLT was defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 as any Grade 3 or 4 hematological or non-hematological toxicity occurring at any dose level until the end of Week 6, and suspected to be reasonably related to the investigational product by the Investigator and/or Sponsor except for allergic/ hypersensitivity reactions and any Grade 3/4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days.

An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.Treatment-related are events which had causal relationship to study drug as assessed by the Investigator and were suspected to be reasonably related to the study drug.

Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log linear trapezoidal rule.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Total body clearance of drug from serum, calculated as CL = dose/AUC0-inf. Where AUC0-inf is area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above lower limit of quantification (LLQ) and λz is elimination rate constant.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as = Dose/(AUC0-inf \*λz) after first infusion. Where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Where AUC0-inf is area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above lower limit of quantification (LLQ) and λz is elimination rate constant.

Ctrough is the concentration prior to study drug administration.

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data.

Observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.

The average serum concentration at steady state, calculated as Cav = AUCtau/tau, where tau is the dosing interval (336 hours).

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (168 hours).

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).

Area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is elimination rate constant.

The peak trough fluctuation over one dosing interval at steady state, calculated as PTF (%) = ( \[ Cmax - Cmin \] / Cav )\*100

Mean residence time of drug in the body calculated as: AUMC0-inf / AUC0-inf, where AUMC0-inf is the area under the first moment curve from time zero to infinity. Where AUC0-inf is area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above lower limit of quantification (LLQ) and λz is elimination rate constant.

Apparent volume of distribution at steady-state was reported. Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

Accumulation ratio for Cmax was calculated as Cmax, after third dose/Cmax, after first dose.

Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at third dose divided by area under the serum concentration-time curve within one complete dosing interval at first dose.

Number of subjects with BOR in each category (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) was reported. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: defined as at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD:defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study.

PFS PCWG1 criteria: time from the day treatment is initiated up to progression (for subject's whose prostate specific antigen \[PSA\] level did not decrease after baseline, progression defined as 50% PSA increase relative to baseline; for subject's whose PSA decreased after baseline, progression defined as 50% PSA increase relative to nadir \[smallest PSA value post-baseline\]. Progression was confirmed if progression criterion was met in next 2 assessments as well.) PFS PCWG2 criteria: time from study entry to disease progression or death. Progression was defined as first appearance of progression according to PSA (for subject's whose PSA decreased after baseline, progression was defined as 25% PSA increase relative to nadir. Progression was confirmed if another assessment measured at least 3 weeks later met the criterion as well; for subject's whose PSA did not decrease after baseline, progression was defined as 25% PSA increase relative to baseline assessed 12 weeks after baseline).

TTP was calculated as the time between the date of imaging for the earliest visit where progressive disease was detected and the first dose date plus 1 day. Participants without event are censored on the date of last tumor assessment.

ECOG performance status measured to assess subject's performance status on a scale of 0 to 4, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair. ECOG performance status was reported in terms of number of subjects with Baseline value vs. worst post-baseline value (i.e. highest score) combination.

ECOG performance status measured to assess subject's performance status on a scale of 0 to 4, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair. ECOG performance status was reported in terms of number of subjects with Baseline value vs. best post-baseline value (i.e. lowest score) combination.

BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf has 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10;'0=No pain and 10=Pain as bad as you can imagine'.Total score is reported as average of individual questions ranges from 0 to 10, with lower scores being indicative of less pain or pain interference.Data was not available for "EMD 525797 250 mg" arm for FUP Weeks 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75 and "EMD 525797 1000 mg" arm for FUP Weeks 47, 51, 55, 59, 63, 67, 71 and "EMD 525797 1500 mg arm" for FUP Weeks 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75 respectively as no subjects were evaluable at the specified FUP visits.

Maximum percent change from Baseline in PSA Level during the study was reported.

Minimum percent change from Baseline in PSA Level during the study was reported.

Merck KGaA, Darmstadt, Germany

Subjects were administered with 250 milligram (mg) of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who were clinically benefitted at the end of Week 6 continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

EMD 525797 250 mg

Subjects were administered with 500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who were clinically benefitted at the end of Week 6 continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

EMD 525797 500 mg

Subjects were administered with 1000 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who were clinically benefitted at the end of Week 6 continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

EMD 525797 1000 mg

Subjects were administered with 1500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who were clinically benefitted at the end of Week 6 continued at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

EMD 525797 1500 mg

Total

Age, Continuous

Sex: Female, Male

Safety analysis set included all subjects who received at least 1 dose of the study medication and had at least 1 follow-up safety measure.

Merck KGaA Communication Center

DLT analysis set: all subjects who experienced any DLT during first 6 weeks, regardless of number of doses of drug administered or who were considered completers (did not discontinue treatment for any reason other than DLT, were compliant, did not deviate in drug administration for more than +/-2 days due to any reason other than related toxicity).

Number of Subjects With Dose Limiting Toxicity (DLT)

TEAEs

Serious TEAEs

Related TEAEs

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs

Pharmacokinetic (PK) analysis set included all subjects who received at least first dose of the study drug according to the protocol and who provided sufficient data for a concentration time profile for EMD 525797.Here "Number of Participants analyzed" signifies those subjects who were evaluable for this outcome measure for each arm, respectively.

Observed Maximum Serum Concentration (Cmax) of EMD 525797 After First Infusion

PK analysis set included all subjects who received at least the first dose of the study drug according to the protocol and who provided sufficient data for a concentration time profile for EMD 525797. Here "Number of Participants analyzed" signifies those subjects who were evaluable for this outcome measure for each arm, respectively.

Observed Maximum Serum Concentration (Cmax) of EMD 525797 After Third Infusion

Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Infusion

Total Body Clearance of Drug From Serum (CL) After First Infusion

Apparent Volume of Distribution During Terminal Phase (Vz) of EMD 525797 After First Infusion

Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 1

Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 3

Trough Serum Concentration (Ctrough) Of EMD 525797 at Week 5

Time to Reach Observed Serum Concentration (Tmax) After First Infusion

Time to Reach Observed Serum Concentration (Tmax) After Third Infusion

Week 1

Week 3

Week 5

Week 8

Week 9

Number of Subjects With Positive Anti-EMD 525797 Antibodies

Subjects were administered with 250 milligram (mg) mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of Week 6 will continue at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

Subjects were administered with 500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of Week 6 will continue at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

Subjects were administered with 1000 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of Week 6 will continue at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

Subjects were administered with 1500 mg of EMD 525797 intravenously over 1 hour every 2 weeks for 6 weeks. Subjects who will be clinically benefitted at the end of Week 6 will continue at the same dose-level until disease progression, intolerance to treatment, withdrawal of consent or if the subject was no longer benefitted from the treatment as per Investigator's discretion.

As per change in planned analysis, it was decided that that the biomarker analysis were not significantly associated with compound administration and thus the data was not collected for this outcome.

Serum Levels of Interleukin 6 (IL-6) and Interleukin 8 (IL-8)

C-Reactive Protein Levels

Apparent Terminal Half-life (t1/2) of EMD 525797 After First Infusion

PK analysis set included all subjects who received at least first dose of the study drug according to the protocol and who provided sufficient data for a concentration time profile for EMD 525797. Here "Number of Participants analyzed" signifies those subjects who were evaluable for this outcome measure for each arm, respectively.

Elimination Rate Constant (λz) of EMD 525797 After First Infusion

Observed Minimum Serum Concentration (Cmin) of EMD 525797 After Third Infusion

Average Serum Concentration at Steady State (Cav) of EMD 525797 After Third Infusion

Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval (AUCtau) of EMD 525797 After First Infusion

Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval (AUCtau) of EMD 525797 After Third Infusion

Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of EMD 525797 After First Infusion

Peak Trough Fluctuation Over One Dosing Interval at Steady State (%PTF) of EMD 525797 After Third Infusion

Mean Residence Time of Drug in the Body (MRT) of EMD 525797 After First Infusion

Apparent Volume of Distribution at Steady State (Vss) of EMD 525797 After Third Infusion

Accumulation Ratio Of Cmax (R_Cmax)

Accumulation Ratio of AUC (R_AUC)

Week 6: CR

Week 6: PR

Week 6: SD

Week 6: PD

Week 19: CR

Week 19: PR

Week 19: SD

Week 19: PD

Overall: CR

Overall: PR

Overall: SD

Overall: PD

Efficacy analysis set included all subjects who received at least 1 dose of the study drug.

Number of Subjects With Best Overall Response (BOR)

PCWG1

PCWG2

Progression-free Survival (PFS) as Per Prostate Cancer Clinical Trials Working Group 1 (PCWG1) and Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Criteria

Subject 1

Subject 2

Efficacy analysis set included all subjects who received at least 1 dose of the study drug. Here "Number of Participants" analyzed signifies those subjects who were evaluable for this outcome measure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prostate Cancer With OligometaSTatic Relapse: Combining Stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736)	NCT03795207	Node; Prostate Bone Metastases Prostate Cancer...	SBRT + Durvalum... SBRT	18 Years -	Institut Cancerologie de l'Ouest
A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis	NCT03258320	Prostate Cancer...	Cabazitaxel, Do...	40 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
Drug-drug Interaction of SHR3680 With Repaglinide and Bupropion	NCT04664725	Prostate Cancer...	Repaglinide, Bu...	45 Years - 75 Years	Jiangsu HengRui Medicine Co., Ltd.
A Study to Determine the Safety, Tolerability, Pharmacokinetics and Dynamic Effects of Different Doses of the Study Drug EMD 525797 in Prostate Cancer	NCT00958477	Prostate Cancer Bone Metastases	EMD 525797	18 Years -	Merck KGaA, Darmstadt, Germany
Drug-drug Interaction of SHR3680 With Repaglinide and Bupropion	NCT04664725	Prostate Cancer...	Repaglinide, Bu...	45 Years - 75 Years	Jiangsu HengRui Medicine Co., Ltd.
C-Acetate PET/CT Imaging to Evaluate Treatment Changes in Prostate Cancer	NCT02715583	Prostate Cancer...	11C-Acetate	18 Years -	Abramson Cancer Center at Penn Medicine
C-Acetate PET/CT Imaging to Evaluate Treatment Changes in Prostate Cancer	NCT02715583	Prostate Cancer...	11C-Acetate	18 Years -	Abramson Cancer Center at Penn Medicine

Spots Global Cancer Trial Database for prostate cancer patients