Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Stomach Neoplasms

Carcinoma

Lung Neoplasms

Adenomatous Polyposis Coli

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Stomach Diseases

Neoplastic Processes

Polyps

Adenomatous Polyps

Adenoma

Syndrome

Neoplastic Syndromes, Hereditary

Intestinal Polyposis

Genetic Diseases, Inborn

Stomach Cancer

Familial Adenomatous Polyposis

MYH-associated Polyposis

Solid Tumors with Any WNT-Pathway Activating Mutations (WPAMs) or Microsatellite Stable (MSS) Colorectal Cancer (Irrespective of WPAM Status)

Microsatellite Stable Colorectal Cancer (Irrespective of WPAM Status)

Non-Small Cell Lung Cancer with a WNT-Pathway Activating Mutation (WPAM) in Adenomatous Polyposis Coli (APC) or Beta-Catenin

Gastric Cancer/Gastroesophageal Junction Carcinoma (GEJ) with a WNT-Pathway Activating Mutation (WPAM) in Adenomatous Polyposis Coli (APC) or Beta-Catenin

Solid Tumors with Any WNT-Pathway Activating Mutations (WPAMs)

FOG-001 will be administered IV once weekly at assigned doses in continuous cycles of 28 days

FOG-001

FOG-001 will be administered IV once weekly at the RP2D dose in continuous cycles of 28 days

Clinical Trial Inquiries

Sunil Sharma, MD

Michael Cecchini, MD

Samuel Klempner, MD

Moh'd Khushman, MD

Shivaani Kummar, MD

Meredith S Pelster, MD

Jordi Rodon Ahnert, MD/PhD

Kyriakos Papadopoulos, MD

Keith Orford, MD, PhD

The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic cancer.

This first-in-human, Phase 1/2, multicenter, open-label, non-randomized dose escalation and expansion study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of FOG-001 in participants with locally advanced or metastatic solid tumors. FOG-001 is a first-in-class direct inhibitor of Beta-catenin, which functions by blocking its interaction with the T-cell factor (TCF) family of transcription factors.

FOG-001 in Locally Advanced or Metastatic Solid Tumors

A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors

Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0

The rate of objective responses (Partial \& Complete) using RECIST v1.1

Rate of Dose Limiting Toxicities (DLTs) across dose levels

Change in tumor Myc expression (on-study compared to baseline)

Best response to treatment using RECIST v1.1

Time from initial objective response (partial response or complete response) to disease progression

Progression Free Survival (PFS) using RECIST v1.1

Fog Pharmaceuticals, Inc.

All Drugs and Chemicals

Immunomodulating Agents

pLADD treatment cycle is once every 3 weeks; starting dose 1×10\^8 colony-forming units (CFU) administered IV over 1 hour, and if tolerated increasing to 1×10\^9 CFU

pLADD

This study will evaluate the safety and tolerability of a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD) treatment in adults with metastatic colorectal cancer.

This single arm study is designed to evaluate the safety and tolerability of a personalized treatment in adults with metastatic colorectal cancer by first analyzing the expression of tumor-associated antigens and then treating the patients with a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD)-based immunotherapy. pLADD is based on the attenuated form of Listeria monocytogenes that has been genetically modified to reduce its ability to cause disease, while maintaining its ability to stimulate a potent immune response. pLADD is manufactured using patient-specific antigens and is therefore individualized to each patient.

Study of Personalized Immunotherapy in Adults With Metastatic Colorectal Cancer

A Phase 1 Safety and Tolerability Study of Personalized Live, Attenuated, Double-Deleted Listeria Monocytogenes (pLADD) Immunotherapy in Adults With Metastatic Colorectal Cancer

Number of patients with treatment-related adverse events as assessed by CTCAE v 4.0

Hanlee P. Ji, MD

Aduro Biotech, Inc.

Microsatellite Instability

Genomic Instability

Antineoplastic Agents

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

MK-3475

Dung Le, MD

This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer and 3. patients with other MSI positive cancers.

Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)

Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

For Cohorts A and B: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

For Cohorts A and B: Immune-related Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation.

For Cohort C: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

For Cohorts A and C: Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.

For Cohorts A and C: PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 20 weeks. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 28 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.

When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 28 weeks. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

Disease Control Rate (DCR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

ORR was used to determine whether MSI is a marker that predicts treatment response. This is the same data presented in outcome measure number 8 (ORR, to test against null of 5%).

Merck Sharp & Dohme LLC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Cohort A: MSI Positive Colorectal Cancer

Cohort B: MSI Negative Colorectal Cancer

Cohort C: MSI Positive Non-Colorectal Cancer

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

It was a pre-specified objective to complete this objective in Cohort A and B only. Per protocol during stages 1 and 2, the study enrollment goal was 25 for Cohort A and B. However, only 24 subjects were enrolled in Cohort A. Additional subjects for this study were enrolled during the second expansion portion of this protocol.

Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2

Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2

It was a pre-specified objective to complete this objective in Cohort C only. Per protocol during stages 1 and 2, the study enrollment goal was 21 for Cohort C. Additional subjects for this study were enrolled during the second expansion portion of this protocol.

Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive Non-colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2

It was a pre-specified objective to complete this objective in Cohort A and C only.

Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Overall Survival (OS)

Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC)

Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity

Progression Free Survival (PFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Does MSI as a Marker Predict Treatment Response

Overall Study

Colonic Neoplasms

Herbal and Botanical

Cola

ctDNA positive Gevokizumab for 1 year (maximum of 13 cycles)

120mg IV on day 1 of every 28-day cycle for 1 year (maximum of 13 cycles)

Gevokizumab

ctDNA monitoring at weeks 8, 12, 24, 36, 48, 60 and 72 unless disease recurrence is documented.

Signatera test

Norman Wolmark, MD

This study will look at the recurrence-free survival of microsatellite-stable (MSS) colon cancer in patients are ctDNA (circulating tumor DNA) positive and treated with gevokizumab.

NSABP FC-12 is a single-arm, multi-centered phase II study to evaluate recurrence-free survival in patients with stage II/III microsatellite-stable (MSS) colon cancer who have undergone curative surgery, adjuvant chemotherapy, are ctDNA (circulating tumor DNA)-positive and treated with gevokizumab.

Patients with stage III resected MSS colon cancer (CRC) who are less than or equal to (≤) 6 weeks after completion of at least 3 months of a standard adjuvant chemotherapy regimen, who are interested in participating in the FC-12 study are eligible for pre-entry ctDNA testing for ctDNA-positivity using the Signatera™ assay via the FC-12 study. Within 6 weeks after completion of adjuvant therapy, stage III patients who have signed the FC-12 Pre-Screening ctDNA consent will have blood and primary tissue samples collected and submitted to Natera for ctDNA evaluation. Commercial ctDNA assay results will not be accepted for study entry. For 150 patients screened in this CRC population, the ctDNA-positivity rate is expected to be approximately 20%.

Note: Patients with stage II MSS colon cancer who were determined to be ctDNA-positive by Natera's Signatera™ commercial assay (i.e., outside of the study) after curative resection may be considered for ctDNA confirmation of ctDNA-positivity via the FC-12 study provided that all the following are met:

* The patient has completed of at least 3 months of a standard adjuvant chemotherapy regimen.
* ctDNA samples will be collected and submitted for ctDNA-positivity confirmation by the Signatera™ assay via the FC-12 study within ≤ 8 weeks after the patient has completed adjuvant chemotherapy.
* The patient otherwise meets eligibility criteria. And,
* the patient will be able to start study therapy within 14 weeks after completion of adjuvant chemotherapy.

All eligible consenting patients who have ctDNA-positivity confirmed via the FC-12 study must begin study therapy within 14 weeks from the completion of adjuvant chemotherapy. Patients will receive gevokizumab (120mg IV) on Day 1 of every 28-day cycle for a maximum of 1 year (e.g., 13 cycles: 1 cycle = 28 days). Patients will continue to receive 13 cycles (1 year) of study therapy unless the patient elects to discontinue study medication, does not adhere to the study per the investigator, experiences intolerable drug toxicity, or has disease recurrence confirmed by imaging.

ctDNA will be monitored at Weeks 8, 12, 24, 36, 48, 60, and 72 unless disease recurrence is documented by imaging. Imaging will include CT scan of chest, abdomen and pelvis and will occur every 24 weeks (6 months) for the duration of the patient's participation in the study or until imaging confirms recurrence.

All patients will be followed for approximately 18 months after initiating study therapy or until imaging confirms recurrence whichever comes first.

The sample size and maximum enrollment for this single arm phase II trial is approximately 31 patients with stage II patient accrual capped at no more than 8 patients. Enrolled patients who withdraw consent prior to receiving study therapy or who are unable to begin study therapy will be replaced.

Safety assessments will occur at intervals per protocol (Section 5.0). Drug toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0).

Submission of archived tumor tissue and blood for FC-12 correlative science studies will be a requirement for all patients enrolled into the study. Serial blood samples will be collected at specified time points throughout the study for gevokizumab pharmacokinetics (PKs) and anti-drug antibody (ADA) assessment.

Stool samples for FC-12 correlative science microbiome studies are optional.

A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy

Percentage of patients alive absent recurrence

Percentage of patients who have converted to negative ctDNA assay at 8 weeks from start of study therapy

Percentage of patients who have converted to a negative ctDNA assay at 8 weeks and are absent recurrence at one year

Percentage of patients who have not converted to a negative ctDNA assay at 8 weeks and are absent a recurrence at one year.

Distribution of patients (percentage) by maximum observed grade of adverse event (0-5).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FOG-001 in Locally Advanced or Metastatic Solid Tumors	NCT05919264	Cancer Colorectal Canc... Solid Tumor Locally Advance... Metastatic Canc... Gastric Cancer Non-small Cell ... Non-small Cell ... Non-small Cell ... Non-small Cell ... Non-Small Cell ... Gastroesophagea... WNT Pathway β-catenin Beta-catenin Adenomatous Pol... APC	FOG-001 FOG-001	18 Years -	Fog Pharmaceuticals, Inc.
Study of Personalized Immunotherapy in Adults With Metastatic Colorectal Cancer	NCT03189030	Colorectal Neop...	pLADD	18 Years -	Aduro Biotech, Inc.
Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)	NCT01876511	MSI Positive Co... MSI Negative Co... MSI Positive No...	MK-3475	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy	NCT05178576	Colon Cancer	Gevokizumab Signatera test	18 Years -	NSABP Foundation Inc

Spots Global Cancer Trial Database for microsatellite stable (mss)