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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05199584
Recruitment Status : Recruiting
First Posted : January 20, 2022
Last Update Posted : May 9, 2023
Sponsor:
Information provided by (Responsible Party):
Endeavor Biomedicines, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumors With PTCH1 Loss-of-function Mutations Drug: ENV-101 (taladegib) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations
Actual Study Start Date : May 24, 2022
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: through study completion, an average of 6 months ]
    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).


Secondary Outcome Measures :
  1. Frequency of Adverse Events (AEs) [ Time Frame: through study completion, an average of 6 months ]
  2. Frequency of unacceptable toxicities [ Time Frame: through study completion, an average of 6 months ]
    Unacceptable toxicities = non-hematologic AEs >= Grade 3 in severity, not including alopecia and fatigue.

  3. ORR by Investigator [ Time Frame: through study completion, an average of 6 months ]
    Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST 1.1.

  4. Clinical Benefit Rate (CBR) [ Time Frame: through study completion, an average of 6 months ]
    CBR = the proportion of patients who achieved CR, PR or stable disease as determined by the treating Investigator using RECIST 1.1.

  5. Overall Survival (OS) [ Time Frame: through study completion, an average of 6 months ]
    OS = Number of months from initiation of study medication to the date of death due to any cause or last follow up.

  6. Duration of Response (DOR) [ Time Frame: through study completion, an average of 6 months ]
    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.

  7. Progression Free Survival (PFS) [ Time Frame: through study completion, an average of 6 months ]
    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.

  8. Change in Gli1 inhibition [ Time Frame: From Baseline through study completion, an average of 6 months ]
    Percentage change in inhibition of Gli1, a marker for inhibition of the Hedgehog pathway, in skin biopsies.

  9. Change in steady-state exposure to study medication [ Time Frame: From Baseline through study completion, an average of 6 months ]
    Measurement of trough concentration of study medication in blood at Baseline and the end of each 28-day treatment cycle


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Females or males greater than or equal to 18 years of age. Females and males between 12 and 17 years of age (inclusive) may be enrolled if deemed appropriate after review of an X-ray with the sponsor for evaluation of growth plate development
  • 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

Exclusion Criteria:

  • 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 OS > 90%) treated with expected curative outcome (prior history of in situ 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 30 days 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 for the duration of the study and for 30 days 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05199584


Contacts
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Contact: Endeavor Clinical Trials 1-858-727-3199 ebmclinical@endeavorbiomedicines.com

Locations
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United States, California
Research Site Recruiting
Los Angeles, California, United States, 90095
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
Research Site Recruiting
San Diego, California, United States, 92037
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
Research Site Recruiting
Santa Rosa, California, United States, 95403
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Florida
Research Site Recruiting
Tampa, Florida, United States, 33609
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Illinois
Research Site Recruiting
Zion, Illinois, United States, 60099
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Louisiana
Research Site Recruiting
Covington, Louisiana, United States, 70433
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Nevada
Research Site Recruiting
Las Vegas, Nevada, United States, 89102
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, New York
Research Site Recruiting
New York, New York, United States, 10065
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, North Carolina
Research Site Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Endeavor Clinical Trials    858-727-3199    ebmlinical@endeavorbiomedicines.com   
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
Research Site Withdrawn
Cleveland, Ohio, United States, 44106
Research Site Recruiting
Columbus, Ohio, United States, 43210
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Pennsylvania
Research Site Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Virginia
Research Site Recruiting
Fredericksburg, Virginia, United States, 22408
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
Research Site Recruiting
Lynchburg, Virginia, United States, 24501
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
United States, Wisconsin
Research Site Recruiting
Madison, Wisconsin, United States, 53792
Contact: Endeavor Clinical Trials    858-727-3199    ebmclinical@endeavorbiomedicines.com   
Sponsors and Collaborators
Endeavor Biomedicines, Inc.
Investigators
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Study Director: Srikanth Pendyala, M.D. Endeavor Biomedicines
More Information
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Responsible Party: Endeavor Biomedicines, Inc.
ClinicalTrials.gov Identifier: NCT05199584    
Other Study ID Numbers: ENV-ONC-101
First Posted: January 20, 2022    Key Record Dates
Last Update Posted: May 9, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Endeavor Biomedicines, Inc.:
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
Additional relevant MeSH terms:
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Neoplasms