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Genital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endometrial Neoplasms

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Natriuretic Agents

All Drugs and Chemicals

Mannitol

Escalating doses of VS-6766 (RO5126766) and Defactinib (VS-6063) were evaluated in patients with advanced solid tumours to establish the recommended phase II dose. Dose escalation followed a 3+3 design with a maximum of four patient cohorts.

This arm is now complete.

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with KRAS mutant NSCLC (20 patients).

This arm is now complete.

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients advanced RAS mutant solid tumours with biopsiable disease (6 patients).

This arm is now complete.

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with LGSOC (20 patients).

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with CRC (10 patients).

This arm is now complete.

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with KRAS G12V mutant NSCLC (10 patients).

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis-related) (10 patients).

The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with pancreatic cancer (10 patients).

VS-6766 will be supplied as 0.8mg hypromellose (HPMC) capsules for oral administration. The capsule fill consists of VS-6766 and the inactive ingredients mannitol and magnesium stearate.

VS-6766 will be administered on a twice weekly (Monday and Thursday or Tuesday and Friday) schedule for 3 weeks followed by 1 week off in every 4 week cycle, under fasting conditions (approximately 1 hour prior or 2 hours after a meal). The starting dose, based on the previous Phase I trial will be 3.2 mg given orally as a single daily dose. This can be escalated to a maximum of 4mg (as per dose escalation rules in the protocol).

VS-6766

Defactinib is formulated as a white to off-white oval tablet for oral administration and supplied in single unit dose strength of 200 mg in 120 cc (HDPE) bottles. In addition to Defactinib, formulation components include microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, and magnesium stearate.

Patients will receive Defactinib orally immediately after a meal twice daily (approximately every 12 hours) for 3 weeks followed by 1 week off in every 4 week cycle. The starting dose will be 200mg. This can be escalated to a maximum of 400mg (as per dose escalation rules in the protocol).

Defactinib

Udai Banerji, FRCP, PhD

This is a multi-centre, investigator-initiated, dose escalation, Phase I trial of the combination of the FAK inhibitor, Defactinib (VS-6063), and the dual RAF/MEK inhibitor, VS-6766 (RO5126766) in patients with advanced solid tumours. VS-6766 (RO5126766) is the same compound as CH5126766.

There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). This will be followed by a dose expansion phase to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.

This is a multi-centre, investigator-initiated, dose escalation, Phase I trial of the combination of the FAK inhibitor, Defactinib, and the dual RAF/MEK inhibitor, VS-6766 in patients with advanced solid tumours.

There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients were enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Up to 24 patients with solid tumours were treated in the dose escalation phase of this study.

The dose escalation phase is now closed to recruitment.

This will be followed by a dose expansion phase of 86 patients to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.

The dose expansion phase is made up of 7 cohorts:

* 20 patients with KRAS mutant non-small-cell lung cancer (NSCLC);
* 7 patients with solid tumours (enriched for those with RAS mutations) willing to undergo biopsies at three time points throughout the study;
* 20 patients with low grade serous ovarian cancer (LGSOC);
* 10 patients with colorectal cancer (CRC);
* 10 patients with KRAS G12V mutant NSCLC;
* 10 patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis related) and
* 10 patients with pancreatic cancer.

The following cohorts are still open to recruitment:

* Patients with low grade serous ovarian cancer (LGSOC);
* Patients with KRAS G12V mutant NSCLC;
* Patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis-related) and
* Patients with pancreatic cancer.

Patients will take the two investigational medicinal products (IMPs) as follows:

VS-6766 will be administered orally twice a week on Monday/Thursday or Tuesday/Friday at least one hour prior or two hours after a meal. The starting dose of VS-6766 will be 3.2mg once a day, twice a week and can be escalated to a maximum of 4mg once a day, twice a week.

Defactinib will be administered orally twice a day immediately after a meal. The starting dose of Defactinib will be 200mg twice daily and can be escalated to a maximum of 400mg twice daily.

A cycle length is 4 weeks (28 days). Combination dosing (VS-6766 and Defactinib) will commence on Cycle 1 Day 1 for 3 weeks followed by one week without either drug in week 4 (i.e. 3 weeks on, 1 week off).

For patients consenting to optional biopsies, a run-in dose of VS-6766 will be administered on a single day anywhere between Days -7 to Day -3 in order to facilitate pharmacodynamic (PD) biomarker analysis. Therefore, for patients undergoing biopsies the first cycle will be 5 weeks long and subsequent cycles will consist of 4 weeks.

If this schedule is not tolerated, alternative schedules may be explored following discussion by the Safety Review Committee.

The dose escalation phase will enrol patients with advanced RAS mutant solid tumours.

In the dose expansion phase, patients are assigned to one of the following cohorts based on their diagnosis:

* KRAS mutant NSCLC cohort
* LGSOC cohort
* RAS mutant CRC cohort
* Advanced RAS mutant solid tumour cohort - patients in this cohort must have biopsiable disease, be willing and consent to undergo biopsies at three time-points.
* KRAS G12V mutant NSCLC cohort
* RAS/RAF mutant endometrioid cohort
* Pancreatic cohort

Non-randomised: Participants are expressly assigned by phase of study and diagnosis.

Phase I Trial of Defactinib and VS-6766.

FRAME: A Phase I Trial of the Combination of Defactinib (VS-6063) (FAK Inhibitor) and VS-6766 (RO5126766) (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours

Determination of disease response by RECIST criteria version 1.1 and collection of data related to progression free survival.

Quantification of biomarkers such as p-MEK, p-ERK and p-FAK, E-cadherin and vimentin and enumeration of T cell populations which express CD8, CD4 and CD25.

Correlation of antitumour activity of the combination of VS-6766 and Defactinib with the detection of putative predictive biomarkers of response and resistance in archival tumours and plasma DNA.

To determine the maximum dose at which no more than 1 of 6 patients at the same dose level experience a drug related toxicity (DLT) as specified in the protocol.

To assess the safety and toxicity profile of VS-6766 and Defactinib. To determine causality and grading severity of each adverse event by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Determination of the PK parameter Cmax of VS-6766 and Defactinib when dosed together.

Determination of the PK parameter terminal half-life of VS-6766 and Defactinib when dosed together.

Determination of the PK parameter area under the curve of VS-6766 and Defactinib when dosed together.

Verastem, Inc.

Institute of Cancer Research, United Kingdom

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Sarcoma

Soft Tissue Sarcoma

Subjects will be given a one-time infusion of AFNT-211 starting at dose level 1 and monitored for 28 days (DLT period). Each cohort will enroll 2-4 subjects at different dose levels for a total of 20 subjects in the escalation portion. The optimal biological dose and recommended phase 2 dose will be determined.

20 subjects with pancreatic ductal adenocarcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

20 subjects with colorectal carcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

20 subjects with non-small cell cancer will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

20 subjects with solid tumors will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

AFNT-211

Shaunica Mitchell

Binaish Khan

Xiomara Menendez

Heinz-Josef Lenz

Chris Hannigan

Joel R Hecht, MD

Salman Punekar, MD

Sophie Hieronymi

Adam Schoenfeld, MD

Rom S Leidner, MD

Megan Barrett

Meredith Pelster, MD

This study is open to adult patients with solid tumors who have a KRAS G12V mutation. This mutation is often found in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and other cancers. The study is for patients whose cancer has spread through the body and for whom previous treatments were not successful or treatment does not exist. Patients must also be positive for HLA-A\*11:01. The purpose of this study is to find the best dose of AFNT-211 that is safe and can shrink tumors in patients. AFNT-211 is an investigational therapy and this is the first time that AFNT-211 is being administered to patients. AFNT-211 is an autologous T cell product which means that it is made from a patient's own T cells. These cells are engineered and grown to recognize the KRAS G12V protein on the cell surface of cancer cells. AFNT-211 is infused into patients after a short course of lymphodepleting chemotherapy. Patients will frequently visit the study site. The doctors there will regularly check the size of the cancer and the patient's health. They will also take note of any unwanted effects. Patients may continue in this study for as long as they benefit from the treatment.

AFNT-211 is a cellular therapy consisting of autologous CD4+ and CD8+ T cells engineered to express a human leukocyte antigen-A (HLA-A)\*11:01-restricted Kirsten rat sarcoma (KRAS) G12V-specific transgenic T cell receptor (TCR), the wildtype CD8α/β coreceptor, and a FAS-41BB switch receptor. AFNT-211 is being developed by Affini-T Therapeutics, Inc. (hereafter, "the Sponsor") for the treatment of patients with malignant solid tumors. The primary purpose of this study is to assess the safety and tolerability of AFNT-211 in subjects who are HLA-A\*11:01 positive with advanced or metastatic cancers that harbor a KRAS G12V mutation, as well as determine the optimal biological dose (OBD) and recommended Phase II dose (RP2D) of AFNT-211 in this population. This study will also evaluate the preliminary anti-tumor activity of AFNT-211.

This is a Phase I, FIH, multicenter, open-label study of AFNT-211 consisting of a dose escalation part and a dose expansion part. During dose escalation the optimal biological dose (OBD) will be determined as well as the recommended phase 2 dose (RP2D). Additional subjects will enroll in expansion cohorts treated at OBD/RP2D found in escalation.

Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor

Quantify the desirability of a dose in terms of toxicity-efficacy tradeoff during the dose escalation portion of the study

This will be selected based on Bayesian optimal interval Phase I/II (BOIN12) design recommendation and the totality of benefit-risk evidence during dose escalation

The incidence of TEAEs will be used to determine safety and tolerability of AFNT-211

The incidence of SAEs will be used to determine safety and tolerability of AFNT-211

The incidence of DLTs during Dose Escalation will be used to determine safety and tolerability of AFNT-211

Percentage of subjects who achieved partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Time from first documentation of response of PR or better to first documentation of disease progression or death from any cause, whichever occurs first.

From enrollment to first documentation of disease progression or death of any cause, whichever occurs first.

Time from first AFNT-211 infusion to first documentation of PR or better.

Percentage of subjects who have achieved PR or CR, or had stable disease (SD) for 6 months or more.

From time of enrollment to death from any cause

Affini-T Therapeutics, Inc.

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Bevacizumab

Immune Checkpoint Inhibitors

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy.

Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy plus Immune checkpoint inhibitors.

Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy, Immune checkpoint inhibitors plus bevacizumab.

Non-small cell lung cancer patients with KRAS mutation were treated from clinical trials.

Non-small cell lung cancer patients with KRAS mutation were not treated for anything.

pemetrexed, 500mg/m2, ivgtt every 21 day.

Chemotherapy.

Yongchang Zhang, MD

Nong Z Yang, MD

Nong Yang, MD

This study aims to analyze the survival condition of different groups about non-small cell lung cancer patients with KRAS mutations. These groups are made according to the treatment regime, brain metastases and KRAS alterations.

This study aims to analyze the survival condition of different groups about non-small cell lung cancer patients with KRAS mutations. These groups are made according to the treatment regime, brain metastases and KRAS alterations.

All the groups were assessed to chemotherapy, chemotherapy plus immunotherapy, clinical trials etc.

Tissue were obtained with the permission from patients.

Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer

Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer Based on NGS Test Results in Hunan Province, China

To assess overall survival, define as first dose to the death of the subject due to any cause.

PFS defines as first dose to first documented disease progression assessed by investigator or death due to any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial of Defactinib and VS-6766.	NCT03875820	NSCLC Low Grade Serou... Endometrioid Ca... Pancreatic Canc...	VS-6766 Defactinib	18 Years -	Institute of Cancer Research, United Kingdom
Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor	NCT06105021	Pancreatic Duct... Non-Small Cell ... Colorectal Canc... Solid Tumor KRAS G12V	AFNT-211	18 Years -	Affini-T Therapeutics, Inc.
Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer	NCT03647098	KRAS G12C Non-small Cell ... KRAS G12D KRAS G12V KRAS G12R KRAS G12Y KRAS G13N	Chemotherapy.	18 Years -	Hunan Province Tumor Hospital

Spots Global Cancer Trial Database for kras g12v

Every month we try and update this database with for kras g12v 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 kras g12v

Every month we try and update this database with for kras g12v 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 kras g12v 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.