Solid Tumors With PTCH1 Loss-of-function MutationsPhase 2NCT05199584
A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations
A Phase 2 study testing ENV-101 (taladegib) in people with Solid Tumors With PTCH1 Loss-of-function Mutations, run by Endeavor Biomedicines, Inc. at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors With PTCH1 Loss-of-function Mutations
- What is being tested?
- ENV-101 (taladegib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 16 sitesUnited States
- Study dates
- 24 May 2022to 20 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Research Site
Cincinnati, Ohio, 45229
Research Site
Columbus, Ohio, 43210
Research Site
Covington, Louisiana, 70433
Research Site
Durham, North Carolina, 27710
Research Site
Fredericksburg, Virginia, 22408
Research Site
Houston, Texas, 77030
Research Site
Las Vegas, Nevada, 89102
Research Site
Los Angeles, California, 90095
Research Site
Lynchburg, Virginia, 24501
Research Site
Madison, Wisconsin, 53792
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10065
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Santa Rosa, California, 95403
Research Site
Tampa, Florida, 33609
Research Site
Zion, Illinois, 60099
About this study
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
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.
- Being tested
- ENV-101 (taladegib)
- 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
- Medical subject headings
- Laryngeal Diseases, Melanoma, Adenoma, Islet Cell, Osteosarcoma, Rhabdomyosarcoma, Sarcoma, Uveal Melanoma, Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENV-101 (taladegib)Drug
tablets dosed once-daily
| Study group | Role | What they receive |
|---|---|---|
| 200 mg ENV-101 | Experimental | ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles Receives: Drug: ENV-101 (taladegib) |
| 300 mg ENV-101 | Experimental | ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles Receives: Drug: ENV-101 (taladegib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: through study completion, an average of 6 months
Secondary outcomes (9)
Frequency of Adverse Events (AEs)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: From Baseline through study completion, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start24 May 2022
- Primary completion20 Feb 2024
- Study completion20 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumors With PTCH1 Loss-of-function MutationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endeavor Biomedicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lisa Lancaster, M.D., Study director, Endeavor Biomedicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199584
- Sponsor's protocol ID
- ENV-ONC-101
- Status last verified
- Mar 2026
- First submitted
- 14 Dec 2021
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05199584
- Acronym / sponsor ID
- ENV-ONC-101
- Keywords
- Patched-1, PTCH1, Hedgehog inhibitor, Smoothened inhibitor, Endeavor, NGS, Next Generation Sequencing, Head and Neck
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Endeavor Biomedicines, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 May 2022 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 20 Feb 2024 (actual)
- First posted
- 20 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 200 mg ENV-101 | Experimental | Drug: ENV-101 (taladegib)ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles |
| 300 mg ENV-101 | Experimental | Drug: ENV-101 (taladegib)ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENV-101 (taladegib)tablets dosed once-daily | Drug | 200 mg ENV-101, 300 mg ENV-101 |
Primary outcome
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).
9 secondary outcomes
Frequency of Adverse Events (AEs)
Time frame: through study completion, an average of 6 months
Frequency of unacceptable toxicities
Time frame: through study completion, an average of 6 months
ORR by Investigator
Time frame: through study completion, an average of 6 months
Clinical Benefit Rate (CBR)
Time frame: through study completion, an average of 6 months
Overall Survival (OS)
Time frame: through study completion, an average of 6 months
Duration of Response (DOR)
Time frame: through study completion, an average of 6 months
Progression Free Survival (PFS)
Time frame: through study completion, an average of 6 months
Change in Gli1 inhibition
Time frame: From Baseline through study completion, an average of 6 months
Change in steady-state exposure to study medication
Time frame: From Baseline through study completion, an average of 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Lancaster, M.D. study director
Endeavor Biomedicines
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ENV-101 (taladegib) in people with Solid Tumors With PTCH1 Loss-of-function Mutations, run by Endeavor Biomedicines, Inc. at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: through study completion, an average of 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.