A Study Evaluating The Safety And Efficacy Of ENV-101 (Taladegib) In Patients With Advanced Solid Tumors Harboring PTCH1 Loss Of Function Mutations

Study Overview

A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

This study employs a 2-stage design that aims to evaluate the efficacy and safety of ENV- 101, a potent Hedgehog (Hh) pathway inhibitor, in patients with refractory advanced solid tumors characterized by loss of function (LOF) mutations in the Patched-1 (PTCH1) gene. Stage 1 of this study will enroll approximately 44 patients randomized between two dose levels. As appropriate, Stage 2 of the study will expand enrollment based on the results of Stage 1.

N/A

Solid Tumors With PTCH1 Loss-of-function Mutations

DRUG: ENV-101 (taladegib)

ENV-ONC-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-12-14	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-12-14
First Submitted that Met QC Criteria 2022-01-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-12-18
First Posted (ACTUAL) 2022-01-20	Results First Posted N/A	Last Verified 2023-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 200 mg ENV-101 ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles	DRUG: ENV-101 (taladegib) tablets dosed once-daily
EXPERIMENTAL: 300 mg ENV-101 ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles	DRUG: ENV-101 (taladegib) tablets dosed once-daily

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 200 mg ENV-101

ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles

DRUG: ENV-101 (taladegib)

tablets dosed once-daily

EXPERIMENTAL: 300 mg ENV-101

ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles

DRUG: ENV-101 (taladegib)

tablets dosed once-daily

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is comprised of Complete Response (CR) and Partial Response (PR), measured by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), as determined by an independent review (confirmed CR or PR will be defined as a repeat assessment performed no less than 28 days after the criteria for response is first met).	through study completion, an average of 6 months

Secondary Outcome Measures	Measure Description	Time Frame
Frequency of Adverse Events (AEs)		through study completion, an average of 6 months
Frequency of unacceptable toxicities	Unacceptable toxicities = non-hematologic AEs >= Grade 3 in severity, not including alopecia and fatigue.	through study completion, an average of 6 months
ORR by Investigator	Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST 1.1.	through study completion, an average of 6 months
Clinical Benefit Rate (CBR)	CBR = the proportion of patients who achieved CR, PR or stable disease as determined by the treating Investigator using RECIST 1.1.	through study completion, an average of 6 months
Overall Survival (OS)	OS = Number of months from initiation of study medication to the date of death due to any cause or last follow up.	through study completion, an average of 6 months
Duration of Response (DOR)	DOR = the number of months from the start of CR or PR, whichever response is recorded first and subsequently confirmed, to the first date that recurrent or progressive disease is documented or death.	through study completion, an average of 6 months
Progression Free Survival (PFS)	PFS = number of months from initiation of study medication to the earlier of disease progression or death due to any cause or last follow up.	through study completion, an average of 6 months
Change in Gli1 inhibition	Percentage change in inhibition of Gli1, a marker for inhibition of the Hedgehog pathway, in skin biopsies.	From Baseline through study completion, an average of 6 months
Change in steady-state exposure to study medication	Measurement of trough concentration of study medication in blood at Baseline and the end of each 28-day treatment cycle	From Baseline through study completion, an average of 6 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Females or males greater than or equal to 18 years of age. If under 18 years of age, males must have a bone age of at least 17 years and females must have a bone age of at least 15 years. X-rays will be reviewed by a qualified physician (e.g. radiologist or endocrinologist) for eligibility for those under 18 years of age
Has histologically or cytologically confirmed solid tumor that harbors a PTCH1 loss of function mutation, identified via genomic sequencing routinely performed at a CLIA certified laboratory
Able to take medication orally
Patients must be refractory to all standard of care therapy, or standard or curative therapy does not exist, or the patient has documented their refusal of standard of care therapies
Patients willing to sign and have a full understanding of the informed consent form
Life expectancy of ≥ 3 months

Concurrent administration of any anti-cancer therapies (e.g., chemotherapy, other targeted therapy) other than those administered in this study
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters are allowed
Malignancies other than the primary tumor type within 5 years prior to study start, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year Overall Survival > 90%) treated with expected curative outcome (e.g., in situ melanoma, basal or squamous cell skin cancer if completely excised, localized prostate cancer that is managed by surveillance, ductal carcinoma in situ treated surgically with curative intent are allowed)
History of clinically significant autoimmune disease requiring prescription systemic therapy in the last two years prior to study start; patients with controlled hypothyroidism may be considered after evaluation by the Investigator.
Presence of active infection at study start or confirmed active human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV)
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to study start, unstable arrhythmias, or unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician
Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption of investigational product
Major surgical procedure within 28 days prior to study start or anticipation of need for a major surgical procedure during the course of the study
Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to study start
Use of drugs that are known moderate or stronger CYP3A4 inhibitors or inducers within 12 days prior to study start
Unresolved toxicity of ≥ CTCAE Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, platinum-induced neurotoxicity and endocrine disease or ailments that are stable)
Males and females of reproductive potential who are sexually active and unwilling to use birth control for the duration of the study and for 3 months after their final study dose
Females that are pregnant or nursing
Females and males that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final study dose
Males who are unwilling to refrain from sperm donation and females who are unwilling to refrain from egg donation for the duration of the study and for 3 months after their final study dose
Patients with a history of a severe allergic reaction, anaphylactic reaction or known hypersensitivity to any component of ENV-101
Patients who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with a study investigative site or the study Sponsor

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Paul Frohna, M.D., Ph.D., Endeavor Biomedicines

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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