Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Neoplasm Metastasis

Stomach Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Transitional Cell

Neoplastic Processes

Stomach Cancer

Pancreatic Cancer

Transitional Cell Carcinoma

The patients will be dosed once weekly (Days 1, 8, 15 and 22) over a 4-week treatment cycle with a 28 day dose-limiting toxicity (DLT) observation period.

OB-002

This is an open-label, non-randomized trial with OB-002 monotherapy dose escalation followed by a dose expansion in patients with metastatic colorectal, pancreatic, gastric, breast, or urothelial cancer who have progressed on two or more treatment regimens.

The dose escalation will use a conventional 3+3 approach, at a minimum of four planned dose levels (0.25, 0.5, 1.0, and 1.5 mg/kg), to establish a maximum tolerated dose (MTD). Additional dose levels may be investigated if PK, pharmacodynamic (PD), safety, and efficacy data indicate higher dose levels may be appropriate. The first patient - sentinel patient - at each dose level will be observed for three days before additional patients can be dosed within the same dose level.

The patients will be dosed once weekly (Days 1, 8, 15, and 22) over a 4-week treatment cycle with a 28-day dose-limiting toxicity (DLT) observation period. After a full cohort has completed Day 28 assessments there will be a pause for safety evaluation conducted by the Safety Monitoring Committee (SMC). Once safety data have been reviewed, the SMC will make their recommendations to Orion who will decide whether to proceed to dosing the next dose cohort. Screening may continue during the SMC pause.

Once all patients in the highest planned cohort (1.5 mg/kg OB 002) have completed Day 28 assessments, safety, PK, receptor occupancy (RO), and tolerability data will be reviewed to determine which dose level should be expanded or whether an additional dose level is needed. The expanded cohort will enrol 6 patients at the identified dose level.

Patients may remain on treatment until disease progression with a follow-up (FU) period of up to 12 months. All adverse events (AEs) and non-invasive tumor assessments will be documented throughout the FU period to characterize the objective response rate (ORR) and, progression-free survival (PFS). Patients that do not complete the DLT observation period for non-DLT reasons will be replaced

A total of up to 36 patients will be screened and 18 enrolled. At least 3 patients at each of the 4 dose levels (0.25, 0.5, 1.0, and 1.5 mg/kg planned) and up to 6 patients at the highest dose(s) if no MTD. An additional 3 patients may be recruited at any of the dose levels to define the dose(s) for further development. Each patient will be enrolled for at least one 28-day cycle of treatment with a FU period of up to 12 months.

Study of OB-002 in Patients With Refractory Metastatic Cancer

A Phase 1b, Open-label, Non-randomized Trial for the Assessment of Safety, Tolerability, and Pharmacokinetics of OB-002 as a Monotherapy in Patients With Refractory Metastatic Colorectal, Pancreatic, Gastric, Breast, or Urothelial Cancer

A number of patients developing antidrug antibodies (ADA) and the titers developed in these participants.

Percent of CCR5 receptors occupied by OB-002 in blood

Percent of CCR5 receptors occupied by OB-002 in tumor biopsies

Objective response rate (ORR): defined as the proportion of patients having best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.

Objective response rate (ORR): defined as the proportion of patients having complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.

Objective response rate (ORR): defined as the proportion of patients having a partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.

Progression-free survival (PFS): defined as the time from randomization until objective tumor progression or death, whichever comes first by RECIST v1.1

Systemic monitoring of circulating immune cells

Systemic monitoring of secreted cytokines.

Systemic monitoring of secreted chemokines.

Examination of tumor-associated immune cells in tumor microenvironment

Genomic analyses on whole blood/peripheral blood mononuclear cells (PBMC) for T-cell repertoire (TCR) analyses

Plasma circulating tumor DNA (ctDNA) analysis

Number of patients experiencing adverse events (AEs), serious AEs (SAEs) abnormalities in clinical laboratory tests, vital signs, electrocardiograms (ECGs), and physical exams

MTD will be defined on the basis of dose-limiting toxicities (DLTs)

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with maximum observed concentration (Cmax) profile of OB-002 in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with time to maximum serum concentration (Tmax) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with area under the curve from time 0 to last sampling time (AUC0-t) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with area under the curve from time 0 to infinity (AUC0 ∞) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with terminal half-life (t1/2) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with the volume of distribution (Vd) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

To evaluate the multiple-dose pharmacokinetic (PK) profile of OB-002 with clearance (CL) in patients with refractory metastatic colorectal, pancreatic, breast, or urothelial cancer.

Orion Biotechnology Polska Sp. z o.o.

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Sarcoma

Acquired Immunodeficiency Syndrome

HIV Infections

Sarcoma, Kaposi

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Communicable Diseases

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Anti-Infective Agents

All Drugs and Chemicals

Ritonavir

Efavirenz

HIV Protease Inhibitors

Protease Inhibitors

Anti-Retroviral Agents

Maraviroc

Etravirine

Tipranavir

Anti-HIV Agents

Antiviral Agents

The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.

FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.

Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.

Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Patrick Unemori, MD

Toby Maurer, MD

The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates.

There is growing evidence that C-C chemokine receptor 5 (CCR5) may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis, encodes viral macrophage inflammatory proteins or vMIP. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor \[5, 6\], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%). This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS. To date, there have been no studies examining the effect of MVC on KS.

There is a need for therapeutic development for KS. Standard of care for KS involves initiation or optimization of antiretroviral therapy. A significant proportion of KS cases do not respond to ART alone, with non-response rates ranging from 25-55%, with response times averaging 9 or more months depending on which patient series is identified. In severe or in cases of KS unresponsive to ART, standard of care involves systemic chemotherapy with liposomal doxorubicin, which is not without adverse reactions. Adverse reactions to liposomal doxorubicin include cardiac toxicity, nausea, vomiting, diarrhea, abdominal pain, fatigue, and patients may require pre-regime tests of varying costs, along with resources and time needed for intravenous infusion. Nonresponse rates for liposomal doxorubicin hover around 20%. Focal cases may be more amenable to radiation therapy or intralesional velban. However, radiation and intralesional therapies are limited to focal sites, require monitored visits and specialized care, can be given only in limited amounts, and carry various adverse effects. With these nonresponse rates, potential adverse reactions, and resources and time needed for therapeutic delivery, there are clear benefits proffered by an effective oral therapy requiring minimal monitoring, as is the case with MVC.

Maraviroc (MVC) is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 (CD4) cells. Maraviroc has demonstrated selective and reversible binding to CCR5, as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes, but has no activity against viruses that enter CD4+ cells using CXCR4. In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications; nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors.

Although there is growing evidence that CCR5, a potential therapeutic target, is involved in KS pathogenesis, to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc (MVC) on KS. As such, the aim of this study is to examine the effect of Maraviroc, a CCR5 inhibitor, on KS.

Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.

Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96.

The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema.

Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.

Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells

Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells

Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells

Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells

Pfizer

ViiV Healthcare

University of California, San Francisco

No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.

The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.

Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.

Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.

Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Treatment Arm (Maraviroc)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Mean duration of Human Immunodeficiency Virus (HIV) diagnosis

Mean duration of Kaposi's Sarcoma (KS) diagnosis

CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells

Mean cluster of differentiation 4 (CD4) count

Number of Kaposi's Sarcoma (KS) Lesions at Baseline

Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up. In the remaining eight patients, either the baseline or final follow-up or both specimens had lower than 80% cell viability and were therefore excluded from immunophenotyping analyses. The small sample sizes reduced the statistical power of the reported results.

Dr. Toby Maurer, MD

Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area

Percent Change in KS Total Surface Area

Only seven patients total had measurable edema at any time during the study

Change in Edema Grade

Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load

Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.

Percent Change in CCR5 Levels on CD4+ T-Cells

Percent Change in CCR5 Levels on CD8+ T-cells

Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells

Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells

Overall Study

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Leronlimab

Leronlimab (PRO 140) will be administered subcutaneously at a weekly dose of 700 mg in combination with staring dose of 80 mg Regorafenib at first week of the Cycle 1, followed by escalation of Regorafenib dose to 120 mg and 160 mg in second and third weeks of Cycle 1, respectively. No Regorafenib will be administered during the fourth week.

leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5

700mg leronlimab weekly dose

Regorafenib is a small-molecule multiple kinase inhibitor

80mg Regorafenib at week 1

120mg Regorafenib at week2

160 mg Regorafenib at week 3

This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

This ia a phase II, single arm study with 30 patients in order to test the hypothesis that the combination of Leronlimab (PRO 140) SC and oral Regorafenib will increase PFS in patients with CCR5 + MSS mCRC.

Leronlimab will be administered subcutaneously at a weekly dose of 700 mg in combination with staring dose of 80 mg Regorafenib at first week of the Cycle 1, followed by escalation of Regorafenib dose to 120 mg and 160 mg in second and third weeks of Cycle 1, respectively. No Regorafenib will be administered during the fourth week.

Leronlimab in Combination With Regorafenib in Patients With CCR5+, Metastatic Colorectal Cancer

A Phase II Study of Leronlimab (PRO 140) in Combination With Regorafenib in Patients With CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of OB-002 in Patients With Refractory Metastatic Cancer	NCT05940844	Metastatic Canc... Metastatic Colo... Metastatic Panc... Metastatic Gast... Metastatic Brea... Metastatic Urot...	OB-002	18 Years -	Orion Biotechnology Polska Sp. z o.o.
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)	NCT01276236	Kaposi's Sarcom...	Maraviroc	18 Years -	University of California, San Francisco
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)	NCT01276236	Kaposi's Sarcom...	Maraviroc	18 Years -	University of California, San Francisco
Study of OB-002 in Patients With Refractory Metastatic Cancer	NCT05940844	Metastatic Canc... Metastatic Colo... Metastatic Panc... Metastatic Gast... Metastatic Brea... Metastatic Urot...	OB-002	18 Years -	Orion Biotechnology Polska Sp. z o.o.
Leronlimab in Combination With Regorafenib in Patients With CCR5+, Metastatic Colorectal Cancer	NCT05730673	CCR5 Microsatellite ... Metastatic Colorectal Canc...	700mg leronlima... 80mg Regorafeni... 120mg Regorafen... 160 mg Regorafe...	18 Years -	CytoDyn, Inc.

Spots Global Cancer Trial Database for ccr5

Every month we try and update this database with for ccr5 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 ccr5

Every month we try and update this database with for ccr5 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 ccr5 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.