Neoplasms

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Vaccinia

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Communicable Diseases

Poxviridae Infections

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All Drugs and Chemicals

Herbal and Botanical

Molgramostim

Sargramostim

Immunologic Factors

Cola

Dose escalation 1e6 pfu/kg bw, 1e7 pfu/kg bw, 3e7 pfu/kg bw of Recombinant Vaccinia GM-CSF JX-594

Intravenous Dose Range: 1x10\^6 pfu/kg, 1x10\^7 pfu/kg, 3x10\^7 pfu/kg Up to 4 intravenous infusions administered over 60 minutes every 2 weeks.

Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)

The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.

Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

A Phase 1b Dose Escalation Study of JX-594 (Thymidine Kinase-Inactivated Vaccinia Virus Plus GM-CSF) Administered by Biweekly (Every Two Weeks) Intravenous Infusion in Patients With Metastatic, Refractory Colorectal Carcinoma

Any of the following treatment related adverse events: Grade 4 toxicity, Grade 3 hematologic toxicity for \> 5 days, Grade 3 non-hematologic toxicities persisting for \> 7 days except for flu-like symptoms that respond to standard therapies.

Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).

Change over time in viral genomes, infectious units, GM-CSF concentration, peripheral white blood cell counts, plasma cytokine measurements, and neutralizing antibodies to JX-594 in blood and/or serum.

Tumor response (Stable, partial, complete, progression) by standard RECIST on CT/MRI. Decrease in tumor blood marker.

Samsung Medical Center

Jennerex Biotherapeutics

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Pembrolizumab

Immunomodulating Agents

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will be administered a checkpoint inhibitor therapy, including but not limited to pembrolizumab, nivolumab, ipilimumab, and atlizumab, at the standard dosing regimen prescribed by their physician. Stool, blood, and urine samples will be collected from patients prior to start of treatment, and at 4 more timepoints over the next 12 months.

Pembrolizumab Injection

Study Coordinator

Esther Jayachandran

Derrick Su, MD

Nikki Denmark

Osama Hlalah, MD

This study is aimed at understanding the impact of gut microbiota on efficacy of cancer therapies, in particular checkpoint inhibitors, and using the resulting information to design microbial immunotherapies. Although animal models are of use to determine the influences of gut and other microbiota on cancer treatment modalities, they are limited due to differences between mouse and human physiology and immunology, as well as the inherent differences in gut microbial populations between the two mammalian organisms. Therefore, samples obtained as donations from human subjects undergoing cancer treatment are of great value for the identification and determination of bacteria and their metabolic processes that are involved in the successful cure and remission of cancer by checkpoint inhibitor therapies.

The objective of this study is to collect 3 samples each of blood, urine, and stool in subjects with cancer. This is a non-interventional, 2 site study in 100 people who are undergoing any type of cancer immunotherapy. Subjects who meet the entry criteria will provide 5 samples each of blood, urine, and stool over a 12-month period.

A growing body of evidence indicates that the composition of the gut microbiome can influence the efficacy of cancer drugs. For example, it has recently been demonstrated that the presence of certain microbes in the gut is correlated with better responsiveness to the new immunotherapy drugs known as checkpoint inhibitors. Providing these particular microbes as a co-therapy may be a way to improve the overall success rate of these drugs. However, very little is currently known about the mechanisms involved in these observed positive effects.

In order to systematically identify how the presence or absence of particular microbes modulates responsiveness to checkpoint inhibitors and other immunotherapy drugs, Persephone Biome is building a biobank comprised of donated samples from a diversity of cancer patients undergoing various anti-cancer treatments. These samples will be analyzed using metabolic models and machine learning approaches to identify microbial species, gene functions, and metabolic pathways that are associated with efficacy and toxicity of treatments. Ultimately, these data will facilitate the development of live biotherapeutics as co-therapies to various cancer drugs.

This is a non-interventional, 2 site study in 100 subjects who are undergoing any type of cancer immunotherapy. It is preferred that enrollment is balanced by sex; however, it is not required. Subjects who meet the entry criteria will provide 5 samples each of blood, urine, and stool over a 12-month period.

During the screening visit, subjects will receive a stool sampling kit and instructions on how and when to collect the stool sample.

Prior to Visit 2, subjects will collect a stool sample and return it to the laboratory with the shipping material provided. At Visit 2 subjects will have blood drawn and urine collected. A stool sampling kit will be dispensed with instructions on how and when to collect the stool sample. Visit 2 must be conducted prior to the start of immunotherapy.

Prior to Visit 3, subjects will collect a stool sample and return it to the laboratory with the shipping material provided. At Visit 3 subjects will have blood drawn and urine collected. A stool sampling kit will be dispensed with instructions on how and when to collect the stool sample.

Prior to Visit 4, subjects will collect a stool sample and return it to the laboratory with the shipping material provided. At Visit 4 subjects will have blood drawn and urine collected. A stool sampling kit will be dispensed with instructions on how and when to collect the stool sample.

Prior to Visit 5, subjects will collect a stool sample and return it to the laboratory with the shipping material provided. At Visit 5 subjects will have blood drawn and urine collected. A stool sampling kit will be dispensed with instructions on how and when to collect the stool sample.

Prior to Visit 6, subjects will collect a stool sample and return it to the laboratory with the shipping material provided. At Visit 6 subjects will have blood drawn and urine collected.

All concomitant medications and adverse events will be recorded. In the event of an adverse event, every effort should be made to collect stool, blood, and urine samples (considered an unscheduled visit).

In the event that a subject discontinues from the study prior to the 12-month visit (Visit 6) all efforts should be made to carry out the assessments for that visit. Visit 6 will also serve as the end of study visit.

Each subject is identified by a unique central identification code that is unique to the study site. This code is only used for study purposes. After informed consent, every person will be given a subject number. The subject code consists of a non interventional study (NIS) code followed by an International Organization for Standardization (ISO) country code, and the subject number. For the duration of the study and afterwards, only the subject's physician will be able to identify the subject based on the subject identification code.

Patient data to be captured in the electronic case report form (eCRF) include demographics, medical history, cancer history, tobacco and alcohol history, diet, prior and concomitant medications, adverse events, and results of tumor scans using the Response Evaluation Criteria in Solid Tumours (iRECIST) criteria.

The trained investigator site staff will enter the data required by the protocol into the eCRFs from source documents (e.g., medical records and study-specific data capture tools as needed) directly into the study database on a central server. All information in the eCRFs must be traceable to these source documents. Data recorded directly into the eCRFs will be defined before study start and the eCRFs will be considered the source data. Clinical Research Associates (CRAs) and a Data Manager will review eCRFs entered by investigational staff for completeness and accuracy. Automatic quality programs check for data discrepancies in the eCRFs and the resulting queries will be notified to the investigational site using an electronic data query process within the Electronic Data Capture (EDC) system. Designated investigator site staff are required to respond to queries and make any necessary changes to the data. Details of the data correction process will be specified in the Data Management Plan. A validated, electronic database will be employed from the EDC system. An audit trail of all changes to this database, including the date, reason for the data change and who made the change, will be maintained within the same database. The audit trail will be part of the archived data at the end of the study.

The complete data management process (data capture, data entry, data validation, checks on plausibility, query handling, data editing after entry, coding, data base closure, etc.) will be defined in advance within a data management plan.

Automatic queries will be defined according to the data management plan. These queries will be auto-generated in the EDC system for data correction and accuracy. Corrections will be entered directly into the system. This procedure will be repeated until all queries are resolved.

The Sponsor will conduct a site visit to verify the qualifications of each investigator, inspect the site facilities, and inform the investigator of responsibilities and the procedures for ensuring adequate and correct documentation. The investigator is required to prepare and maintain adequate and accurate case histories designed to record all observations and other data pertinent to the study for each study participant. All information recorded on the eCRFs for this study must be consistent with the subjects' source documentation (i.e., medical records).

Stool, blood, and urine specimens from each patient

Development and Analysis of a Stool Bank for Cancer Patients

Development and Analysis of a Sample Bank (Blood, Urine, and Stool) for Cancer Patients, Enabling the Systematic Study of the Effect of Blood, Urinary Tract, and Gut Microbiomes on Response to Treatment

Response of the tumor to treatment, as evaluated by the iRECIST criteria

Pharm-Olam International

Persephone Biosciences

Neoplasm Metastasis

Antibodies

Tislelizumab

Immunoglobulins

Enzyme Inhibitors

JDQ443 in combination with TNO155 and tislelizumab

JDQ443

TNO155

tislelizumab

Novartis Pharmaceuticals

Obi Okafor

Conor E. Steuer

Rebecca Heist

Teresa Song

Rachel Sanborn

Lorenzo Sellitto

Timothy Burns

Shari A Daniels

Marcelo Vailati Negrao

This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.

Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment

All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).

Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.

Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment.

Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to all groups except the brain metastasis group.

OIRR per mRANO-BM is defined as the proportion of participants with a best overall intracranial response (BOIR) of CR or PR according to mRANO-BM criteria, and will be summarized along with the corresponding 90% and 95% exact CI. Applies to brain metastasis group only.

All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs). Applies to JDQ443 dose randomization group only.

Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions. Applies to JDQ443 dose randomization group only.

Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only

Overall response rate is defined as the proportion of patients with BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to JDQ443 dose randomization group only

Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI)

BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.

Per RECIST 1.1, PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death. If patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. PFS will be summarized using the Kaplan-Meier method, along with 95% CI

Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. Estimates will use Kaplan-Meier method, and median DOR and corresponding 95% CI will be presented.

The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. It will be summarized along with the corresponding 95% exact CI

AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab

Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.

Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.

To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D

IDCR is the proportion of participants with a confirmed BOIR of CR or PR or SD (or non-CR/non-PD) per mRANO-BM criteria. It will be summarized along with the corresponding 90% and 95% CI. Applies to the brain metastasis group only.

BOIR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence per mRANO-BM, or until patient comes off study, whichever comes first. BOIR will be summarized along with the corresponding 95% exact CI. Applies to the brain metastasis group only.

IPFS is defined as the time from the date of start of treatment to the date of the first documented progression per mRANO-BM, or death due to any cause. If a patient has not had an event, IPFS will be censored at the date of last adequate tumor assessment. IPFS will be summarized using the Kaplan-Meier method. Median IPFS and IPFS probability at pre specified time-points will be presented along with 95% CI. Applies to the brain metastasis group only.

DOIR is defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression as per mRANO-BM criteria as assessed by central review or date of death due to underlying cause of cancer. DOIR will be summarized using the KM method if data permit. Median DOIR, with corresponding 95% CI. KM estimates for DOIR proportions at specific time points, along with 95% CI will also be provided. Applies to the brain metastasis group only.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma	NCT01380600	Carcinoma, Colo...	Recombinant Vac...	18 Years -	SillaJen, Inc.
Development and Analysis of a Stool Bank for Cancer Patients	NCT04291755	Carcinoma, Non-... Carcinoma, Colo...	Pembrolizumab I...	18 Years -	Persephone Biosciences
Development and Analysis of a Stool Bank for Cancer Patients	NCT04291755	Carcinoma, Non-... Carcinoma, Colo...	Pembrolizumab I...	18 Years -	Persephone Biosciences
Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation	NCT04699188	KRAS G12C Mutan... Carcinoma, Non-... Carcinoma, Colo... Cancer of Lung Cancer of the L... Lung Cancer Neoplasms, Lung Neoplasms, Pulm... Pulmonary Cance... Pulmonary Neopl...	JDQ443 TNO155 tislelizumab	18 Years -	Novartis

Spots Global Cancer Trial Database for carcinoma, colorectal