Clinical trial NCT05199584: A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Endeavor Biomedicines, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-20
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

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 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
measure: Frequency of Adverse Events (AEs)
timeFrame: through study completion, an average of 6 months
measure: Frequency of unacceptable toxicities
timeFrame: through study completion, an average of 6 months
measure: ORR by Investigator
timeFrame: through study completion, an average of 6 months
measure: Clinical Benefit Rate (CBR)
timeFrame: through study completion, an average of 6 months
measure: Overall Survival (OS)
timeFrame: through study completion, an average of 6 months
measure: Duration of Response (DOR)
timeFrame: through study completion, an average of 6 months
measure: Progression Free Survival (PFS)
timeFrame: through study completion, an average of 6 months
measure: Change in Gli1 inhibition
timeFrame: From Baseline through study completion, an average of 6 months
measure: Change in steady-state exposure to study medication
timeFrame: From Baseline through study completion, an average of 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Zion
country: United States
facility: Research Site
state: Illinois
city: Covington
country: United States
facility: Research Site
state: Louisiana
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fredericksburg
country: United States
facility: Research Site
state: Virginia
city: Lynchburg
country: United States
facility: Research Site
state: Virginia
city: Madison
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Endeavor Biomedicines
name: Paul Frohna, M.D., Ph.D.
role: STUDY_DIRECTOR
References: