Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antipyretics

Analgesics

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Acetaminophen

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Durvalumab

Immunoglobulins

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Subjects received PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W \[equivalent to 450 mg Q4W\] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m\^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12.

Subjects received PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m\^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12.

Subjects received PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m\^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12.

Subjects received the MTD determined in Phase 1 (Dose Level +1), comprising PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment.

Durvalumab is administered as an IV infusion over 60 ± 5 minutes.

PLD was administered as an IV infusion in accordance with local prescribing information.

Pegylated Liposomal Doxorubicin

Motolimod was administered as an SC injection. Within 30 minutes prior to each dose of motolimod, subjects were administered 650-1000 mg acetaminophen by mouth to help mitigate potential adverse events (AEs) commonly associated with the administration of motolimod (e.g., fever, myalgia). On days with concurrent motolimod and durvalumab dosing, motolimod administration occurred 30-60 minutes after the end of the durvalumab infusion. After completion of Phase 1, a protocol amendment was implemented to remove motolimod dosing from the study.

Motolimod

George Coukos, MD, PhD

Bradley J Monk, MD

This is an ongoing Phase 1/2, open-label, multicenter, non-randomized study of MEDI4736 (durvalumab) in subjects with recurrent, platinum-resistant ovarian cancer who are scheduled to receive pegylated liposomal doxorubicin (PLD).The primary objective of Phase 1 is to determine the maximum tolerated dose (MTD) and safety profile, with a secondary objective to evaluate the clinical efficacy as measured by progression-free survival (PFS) rate at 6 months (PFS-6). The primary objective of Phase 2 is the evaluation of clinical efficacy as measured by PFS-6. For both phases, secondary objectives include evaluation of clinical efficacy as measured by overall response rate, PFS, and overall survival (OS), safety and tolerability, and immunological responses.

In the completed Phase 1 part of the study, eligible subjects were enrolled using a standard 3 + 3 design to identify the MTD (i.e., the highest dose for which fewer than 33% of subjects experienced a dose-limiting toxicity \[DLT\]) of combination study treatment. All dose levels in Phase 1 included intravenous (IV) PLD (40 mg/m\^2) in combination with subcutaneous (SC) motolimod (2.0 or 2.5 mg/m\^2), using a starting dose of 3 mg/kg of IV durvalumab given every 2 weeks (Q2W) or 1500 mg of IV durvalumab given every 4 weeks (Q4W). All subjects in a cohort had their safety data reviewed for DLTs before proceeding with cohort expansion.

After completion of Phase 1 and determination of the durvalumab MTD to be carried forward into Phase 2, availability of data from another study (NCT01666444) indicated a lack of additive efficacy when motolimod was administered with PLD compared with PLD alone. As such, motolimod dosing was discontinued for all subjects in Study LUD2014-001 after completion of Phase 1. Subjects who had initiated treatment may have continued to receive PLD and durvalumab at their respective dose levels but must have discontinued motolimod. Thus, in the fully-accrued but ongoing Phase 2 portion of the study, subjects received only PLD (40 mg/m\^2) in combination with durvalumab at the MTD determined in Phase 1 (1500 mg every 4 weeks \[Q4W\]).

Subjects are treated in the Core Study for an initial 12 cycles (28 days each) according to their treatment assignment. Durvalumab treatment may be extended for subjects who complete the Core Study with stable disease or better and upon agreement among the subject, Sponsor, and Investigator; extended durvalumab monotherapy may continue until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met.

Subjects are followed on study for 90 days after the last drug administration and off study every 3 months for 3 years from the date of the first dose of study treatment.

Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer

Phase 1/2 Study of Chemoimmunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) + Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin is Indicated

The primary endpoint in Phase 1 and a secondary endpoint in Phase 2 is the safety/tolerability of study treatment. Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. Treatment-emergent AEs are those that occurred or worsened after administration of the first dose of study treatment.

PFS-6 according to RECIST 1.1 is the primary endpoint in Phase 2 and a secondary endpoint in Phase 1, where PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009).

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Eisenhauer et al 2009).

PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression does not occur. Per RECIST 1.1, PD is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009).

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria (Bohnsack et al 2014).

PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014).

After completion of treatment, all subjects are followed for survival every 3 months for up to 3 years following initiation of study treatment or or for subjects continuing treatment, completion of study treatment whichever was longer. OS is measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up are censored on the date when they were last known to be alive.

MedImmune LLC

Celgene

Cancer Research Institute, New York City

Ludwig Institute for Cancer Research

AE documentation includes onset/resolution dates, severity using the NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms are counted only once per subject at the maximum reported grade.

Phase 1, Dose Level 0a

Phase 1, Dose Level 0b

Phase 1, Dose Level +1

Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment.

Phase 2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Switzerland

Region of Enrollment

PS 0 = Fully active, able to carry on all pre-disease performance without restriction; PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; PS 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; PS 3 = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; PS 4 = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; PS 5 = Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline

The population comprises all subjects who received at least one dose of study treatment.

Jonathan Skipper PhD

Any TEAE

TEAE related to any study treatment

TEAE related to durvalumab

TEAE related to PLD

TEAE related to motolimod

Serious TEAE

Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

Progression-free Survival Rate at 6 Months (PFS-6) by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Estimated Using the Kaplan-Meier Method

Number of Subjects With Best Overall Tumor Response by RECIST 1.1

Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method

PFS-12 by RECIST 1.1 as Estimated Using the Kaplan-Meier Method

irCR

irPR

irSD

irPD

Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

PFS-6 by irRECIST as Estimated Using the Kaplan-Meier Method

PFS-12 by irRECIST as Estimated Using the Kaplan-Meier Method

Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method

Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method

Subjects received pegylated liposomal doxorubicin (PLD) (40 mg/m\^2 intravenously \[IV\] on Day 1 of every cycle) + durvalumab (3 mg/kg every 2 weeks \[Q2W, equivalent to 450 mg every 4 weeks (Q4W)\] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m\^2 subcutaneous \[SC\]) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12.

Subjects received the maximum tolerated dose (MTD) determined in Phase 1, comprising PLD (40 mg/m\^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment.

Overall Study

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Nivolumab

Immune Checkpoint Inhibitors

Nivolumab IV every 2 weeks and Motolimod IT injection weekly

Nivolumab IV every 2 weeks and Motolimod SC injection weekly

VTX-2337

Bristol-Myers Squibb

This is an open label, Phase 1b pre-operative window of opportunity biomarker trial to analyze the combination of intravenous (IV) anti-PD-1 inhibitor, nivolumab, given along with toll-like receptor 8 (TLR 8) agonist motolimod delivered either subcutaneously (SC) or by intratumoral injection (IT) in subjects with squamous cell carcinoma of the head and neck (SCCHN). Subjects with previously untreated, resectable SCCHN, will be recruited onto this trial and will initially undergo pre-treatment diagnostic imaging and biological sample collection. These subjects will undergo pre-operative study treatment for a 3 to 4-week period prior to a scheduled surgical resection.

A Study to Evaluate Immune Biomarker Modulation in Response to VTX-2337 in Combination With an Anti- PD-1 Inhibitor in Head and Neck Cancer

A Phase 1b Multicenter Pre-Surgical Study to Evaluate Immune Biomarker Modulation in Response to Motolimod (VTX-2337) in Combination With Nivolumab in Subjects With Resectable Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Tumor immune modulation will be evaluated by counting the number of tumor infiltration CD8+ T cells before and after treatment.

Study will evaluate the number of patients who experience adverse events that lead to a significant delay in surgical resection.

Subject will be monitored for AEs both during treatment and for a specified period after last dose of study treatment. AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer	NCT02431559	Ovarian Cancer	Durvalumab Pegylated Lipos... Motolimod	18 Years -	Ludwig Institute for Cancer Research
Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer	NCT02431559	Ovarian Cancer	Durvalumab Pegylated Lipos... Motolimod	18 Years -	Ludwig Institute for Cancer Research
A Study to Evaluate Immune Biomarker Modulation in Response to VTX-2337 in Combination With an Anti- PD-1 Inhibitor in Head and Neck Cancer	NCT03906526	Carcinoma, Squa...	VTX-2337 Nivolumab	18 Years -	Celgene

Spots Global Cancer Trial Database for motolimod

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

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