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

NCT05199584 | Completed Phase 2 FDA Drug

• 1 other identifier: ENV-ONC-101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Solid Tumors With PTCH1 Loss-of-function Mutations

Keywords

Patched-1; PTCH1; Hedgehog inhibitor; Smoothened inhibitor; Endeavor; NGS; Next Generation Sequencing; Head and Neck; Laryngeal; Hypopharyngeal; Nasal Cavity; Nasopharyngeal; Oral Cavity; Oropharyngeal; Throat; Salivary Gland; Lung; Lung Carcinoid; Breast; Skin; Basal; Squamous; Melanoma; Merkel Cell; Anal; Bile Duct; Colorectal; Esophagus; Gallbladder; Gastrointestinal; Liver; Pancreatic; Pancreatic Neuroendocrine Tumor; NET; Small Intestine; Stomach; Cervical; Endometrial; Ovarian; Penile; Prostate; Testicular; Uterine; Vaginal; Vulvar; Bone; Osteosarcoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Eye; Ocular Melanoma; Retinoblastoma; Brain; Spinal Cord; Neuroblastoma; Adrenal; Pituitary; Bladder; Kidney; Medulloblastoma; Glioma; Wilms; Precision Oncology; Mesothelioma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Frequency of Adverse Events (AEs)

  through study completion, an average of 6 months

• Frequency of unacceptable toxicities

  through study completion, an average of 6 months

• ORR by Investigator

  through study completion, an average of 6 months

• Clinical Benefit Rate (CBR)

  through study completion, an average of 6 months

• Overall Survival (OS)

  through study completion, an average of 6 months

Study Arms (2)

200 mg ENV-101

EXPERIMENTAL

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

Drug: ENV-101 (taladegib)

300 mg ENV-101

EXPERIMENTAL

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

Drug: ENV-101 (taladegib)

Interventions

ENV-101 (taladegib) DRUG

tablets dosed once-daily

200 mg ENV-101; 300 mg ENV-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Endeavor Biomedicines, Inc.: lead

Study Sites (16)

Research Site

Los Angeles, California, 90095, United States

Location

Research Site

Santa Rosa, California, 95403, United States

Location

Research Site

Tampa, Florida, 33609, United States

Location

Research Site

Zion, Illinois, 60099, United States

Location

Research Site

Covington, Louisiana, 70433, United States

Location

Research Site

Las Vegas, Nevada, 89102, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Durham, North Carolina, 27710, United States

Location

Research Site

Cincinnati, Ohio, 45229, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Fredericksburg, Virginia, 22408, United States

Location

Research Site

Lynchburg, Virginia, 24501, United States

Location

Research Site

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Laryngeal Diseases; Melanoma; Adenoma, Islet Cell; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Uveal Melanoma; Retinoblastoma; Neuroblastoma; Pituitary Diseases; Medulloblastoma; Glioma; Mesothelioma

Interventions

LY2940680

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Pancreatic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Neoplasms, Neuroepithelial; Retinal Neoplasms; Eye Diseases, Hereditary; Retinal Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Mesothelial

Study Officials

• Lisa Lancaster, M.D.

  Endeavor Biomedicines

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: January 20, 2022
• Study Start: May 24, 2022
• Primary Completion: February 20, 2024
• Study Completion: February 20, 2024
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)