Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphosarcoma

AK117 monotherapy intravenous (IV) infusion - Weekly doses

An intravenous (IV) infusion of AK117 as monotherapy. All subjects will receive 4 weekly infusions (Days 1, 8, 15, and 22) of AK117 in each 28-day treatment cycle until unacceptable toxicity, documentation of confirmed progressive disease (PD), or subject withdrawal

AK117

Jiong Wu, MD

This is a multicenter, open label, single arm, Phase 1，dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacodynamics, PK, immunogenicity, and preliminary antitumor activity of AK117 administered intravenously to adult subjects with relapsed/refractory advanced or metastatic solid tumors or lymphomas.

The study comprises a dose escalation phase and a dose expansion phase. The phases will be conducted sequentially. Approximately 162 subjects will be enrolled in this study.

A Phase 1 Dose Escalation and Expansion Study of AK117

A Multicenter, Phase 1, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 in Subjects With Advanced Solid Tumors or Lymphomas

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.

DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications .

ORR defined as the proportion of subjects who achieves a best overall response of CR or PR, assessed by Investigator per RECIST Version 1.1 for solid tumor or the Lugano 2014 Classification for lymphoma

The DCR is defined as the proportion of subjects with CR, PR, or SD .

The endpoints for assessment of PK of AK104 include serum concentrations of AK117 at different timepoints after AK117 administration.

The immunogenicity of AK117 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Akeso

Respiratory Tract (Lung and Bronchial) Diseases

Heart and Blood Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia

Lymphoma, Non-Hodgkin

Hodgkin Disease

Precancerous Conditions

Leukemia-Lymphoma, Adult T-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Leukemia, T-Cell

Leukemia, Lymphoid

Hodgkin Lymphoma

All Drugs and Chemicals

Immunomodulating Agents

Patients with cancer or a premalignant condition or at risk of cancer from an immunodeficiency

Scott M Norberg, D.O.

Background:

Cancer has a major impact in the United States and across the world. In 2015, over 1.5 million new cases of cancer were diagnosed in the U.S. Researchers want to study samples from people with cancer or a pre-malignant condition. They hope to develop more effective treatments.

Objective:

To better understand the biology of malignancies and why certain cancers respond differently to treatment.

Eligibility:

Adults at least 18 years old with cancer or a pre-cancerous condition.

Design:

Participants will be screened with a medical history, physical exam, and blood tests. Their diagnosis will be confirmed by the NCI Laboratory of Pathology.

Participants will send tissue blocks or slides from their original tumor biopsy.

At least once, participants will have a medical history, physical exam, and blood and urine tests.

Participants may have the following tests. They may have them more than once:

Apheresis. A needle in one arm removes blood. Blood is run through a machine and the sample cells are taken out. The rest of the blood is returned by a needle in the other arm.

Bone marrow aspiration and biopsy. The hipbone will be numbed. A needle will be put into the hipbone. Bone marrow will be taken out through the needle.

Piece of cancer tissue taken by a needle and syringe.

Computed tomography (CT) scan, magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan or ultrasound to help locate their tumor. For the scans, they lie in a machine that takes pictures.

A small piece of skin removed.

Participants will be contacted by phone once a year to find out how they are doing.

Background:

-Immunotherapy is a promising approach to the treatment of cancer. CIO investigators are studying immunotherapy for the treatment of diverse malignant and premalignant conditions. These studies require the collection of biospecimens for research purposes.

Objectives:

* To collect and bank blood, apheresis products, tumor, body fluids, and other biospecimens from patients with cancer or a premalignant disease or at risk of cancer from an immunodeficiency.
* To collect and bank biospecimens as directed by companion CIO immunotherapy clinical trial protocols.
* To conduct nucleic acid, protein, and immunological and biological research studies on samples collected.

Eligibility:

-Patients must be 18 years of age or older with a diagnosis of cancer or a premalignant condition or an immunodeficiency that increases the risk of being diagnosed with a cancer or premalignant condition.

Design:

* Up to 500 subjects will be enrolled.
* Patients will undergo sampling of blood, apheresis products, tumor, effusions, ascites, urine, bone marrow, serum, plasma, skin, mucosa, or other tissues for banking and laboratory studies.
* No investigational or experimental therapy will be given as part of this protocol.

Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Biospecimen collection for study and understanding of disease.

Correlation of these characteristics with disease.

National Cancer Institute (NCI)

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Stomach Neoplasms

Esophageal Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cholangiocarcinoma

Carcinoma, Renal Cell

Liver Neoplasms

Head and Neck Neoplasms

Carcinoma, Transitional Cell

Fallopian Tube Neoplasms

Neoplasms, Glandular and Epithelial

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal 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

Adenocarcinoma

Fallopian Tube Diseases

Liver Diseases

Stomach Cancer

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Bile Duct Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Fallopian Tube Cancer

Antibodies

Antibodies, Bispecific

Immunoglobulins

Dose-escalation phase: Eligible patients will receive treatment, based on cohort assigned, in 2-week cycles until progression or intolerance.

Expansion phase: Patients enrolled in the expansion phase of the study will receive CDX-585 at the dose level chosen during the escalation phase.

CDX-585 is administered by infusion every 2 weeks

CDX-585

Celldex Therapeutics

Emilie Ginovker

Amy Whitaker

Phase 1 Clinical Research Team

Tara Foote

This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in patients with selected solid tumors.

This study will determine the maximum tolerated dose of CDX-585 while also evaluating the safety, tolerability, and efficacy of CDX-585 in patients with cancer.

Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-585. The dose-escalation part of the study will test the safety profile of CDX-585 and determine which dose of CDX-585 will be studied in the expansion portions of the study.

Approximately 130 patients will be enrolled. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

The expansion portion of the study will further evaluate the safety of CDX-585 in selected tumor types at the dose level chosen during the escalation part of the study.

A Study of CDX-585 in Patients With Advanced Malignancies

A Phase 1 Dose-escalation and Expansion Study of the PD-1 x ILT4 Bispecific Antibody CDX-585 in Patients With Advanced Malignancies

The rates of drug-related adverse events will be summarized, and maximum tolerated dose will be determined.

The rates of drug-related adverse events will be summarized, and further evaluated in specific tumor types.

The rates of drug-related adverse events will be summarized and evaluated.

The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)

The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months

The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented

The time from start of study drug to time of progression or death, whichever occurs first

The time from start of study drug to death

CDX-585 serum concentrations will be measured at specified visits

Samples will be obtained for assessment of human anti-CDX-585

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants received FLX475 tablets orally and ipilimumab by IV infusions

FLX475

William Ho, MD, PhD

This clinical trial is a Phase 2, open-label study to determine the anti-tumor activity of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-programmed cell death 1 (anti-PD-1) or anti-programmed cell death ligand 1 (anti-PD-L1) agent.

The study will be conducted starting with a safety run-in portion in which 6 eligible subjects will be enrolled and treated for at least one 3-week cycle to determine if the safety profile of FLX475+ipilimumab is acceptable to complete enrollment of the approximately 20-subject study.

FLX475 in Combination With Ipilimumab in Advanced Melanoma

Phase 2 Study of FLX475 in Combination With Ipilimumab in Advanced Melanoma

To evaluate the objective response rate (ORR), defined as confirmed complete or partial response per RECIST 1.1, of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-PD-1 or anti-PD-L1 agent

Number of participants that experienced Other Adverse Events

Number of participants that experienced Serious Adverse Events

To evaluate the progression-free survival (PFS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent

To evaluate the overall survival (OS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent

To evaluate the plasma concentrations of FLX475 when it is given in combination with ipilimumab

To assess the effects of FLX475 in combination with ipilimumab on pharmacodynamic (PD) markers relating to drug mechanism of action

To characterize the onset, magnitude, and duration of tumor control in subjects receiving FLX475 in combination with ipilimumab

RAPT Therapeutics, Inc.

Adverse events were reported by the sites into an electronic data capture system

Participants received FLX475 tablets orally and ipilimumab by IV infusions

FLX475: Tablet

Ipilimumab: IV infusion

FLX475 and Ipilimumab Combination Therapy

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The study was terminated early due to changes in the treatment landscape of melanoma that have occurred since the initiation of the study, leading to small numbers of subjects analyzed.

William Ho

This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety,

Objective Response Rate

Safety and Tolerability as Measured by Number of Participants That Experienced Other Adverse Events

This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety.

Progression-free Survival

All participants who received the study drug

Overall Survival (OS)

Plasma Concentrations of FLX475

Pharmacodynamic (PD) Markers

Tumor Control

Safety and Tolerability as Measured by Number of Participants That Experienced Serious Adverse Events

Overall Study

Symptoms and General Pathology

Death

Antibodies, Monoclonal

Gemcitabine

Cisplatin

Immunoglobulins, Intravenous

Dose Escalation, Stage 1: JTX-8064 Monotherapy. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies.

Dose Escalation, Stage 2: JTX-8064 in combination with pimivalimab. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies.

Cohort will enroll subjects with advanced/metastatic PD-1/PD-L1 (PD-(L)1)-naïve, platinum-resistant ovarian cancer.

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced clear cell renal cell carcinoma (ccRCC).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced triple negative breast cancer (TNBC).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, PD-L1+ head and neck squamous cell carcinoma (HNSCC).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, platinum-resistant ovarian cancer.

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced non-small cell lung cancer (NSCLC).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced cutaneous squamous cell carcinoma (cSCC).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS).

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with PD-(L)1i-experienced HNSCC.

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with biliary tract cancer (BTC), including intra-and extra-hepatic biliary duct cancer and cancer of the gallbladder. All subjects must have progressed on or after gemcitabine/cisplatin (Gem/Cis) in the metastatic setting, must have PD-(L)1i resistance.

JTX-8064

pimivalimab

Stew Kroll

JTX-8064-101 is a Phase 1/2, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of JTX-8064 alone and in combination with a PD-1 inhibitor (PD-1i).

JTX-8064 is a humanized mAb designed to block the interaction of LILRB2 with its known ligands, endogenous major histocompatibility complex class I (MHC I) molecules. This is a Phase 1/2, first in human, open label, multicenter, dose escalation and dose expansion clinical trial to determine the safety, tolerability, maximum tolerated dose (MTD) and RP2D of JTX-8064 when administered as a single agent and in combination with a PD-1i in adult subjects with advanced refractory solid tumor malignancies. Additionally, the study will seek to evaluate the pharmacokinetics and immunogenicity of JTX-8064, and preliminary efficacy of JTX-8064 as a monotherapy and in combination with a PD-1i.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1 Dose Escalation and Expansion Study of AK117	NCT04728334	Neoplasms Malig...	AK117	18 Years - 75 Years	Akeso
Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols	NCT02682667	Multiple Myelom... Lymphoma, Non-H... Leukemia-Lympho... Hodgkin Disease Non-Small Cell ...		18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Study of CDX-585 in Patients With Advanced Malignancies	NCT05788484	Non-small Cell ... Gastric Cancer Head and Neck C... Ovarian Cancer Primary Periton... Fallopian Tube ... Bladder Urothel... Colorectal Canc... Esophageal Canc... Hepatic Cancer Renal Cell Carc... Cholangiocarcin... Pancreatic Canc... Other Solid Tum...	CDX-585	18 Years -	Celldex Therapeutics
FLX475 in Combination With Ipilimumab in Advanced Melanoma	NCT04894994	Advanced Melano...	FLX475 Ipilimumab	18 Years -	RAPT Therapeutics, Inc.
Study of JTX-8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors	NCT04669899	Cancer	JTX-8064 pimivalimab	18 Years -	Jounce Therapeutics, Inc.
Study of JTX-8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors	NCT04669899	Cancer	JTX-8064 pimivalimab	18 Years -	Jounce Therapeutics, Inc.
Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols	NCT02682667	Multiple Myelom... Lymphoma, Non-H... Leukemia-Lympho... Hodgkin Disease Non-Small Cell ...		18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Phase 1 Dose Escalation and Expansion Study of AK117	NCT04728334	Neoplasms Malig...	AK117	18 Years - 75 Years	Akeso
A Study of CDX-585 in Patients With Advanced Malignancies	NCT05788484	Non-small Cell ... Gastric Cancer Head and Neck C... Ovarian Cancer Primary Periton... Fallopian Tube ... Bladder Urothel... Colorectal Canc... Esophageal Canc... Hepatic Cancer Renal Cell Carc... Cholangiocarcin... Pancreatic Canc... Other Solid Tum...	CDX-585	18 Years -	Celldex Therapeutics
Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols	NCT02682667	Multiple Myelom... Lymphoma, Non-H... Leukemia-Lympho... Hodgkin Disease Non-Small Cell ...		18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

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