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Open-Label Proof of Concept Study of LTX-315 in Basal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT05188729
Recruitment Status : Recruiting
First Posted : January 12, 2022
Last Update Posted : September 15, 2022
Sponsor:
Collaborators:
Instat Clinical Research
HeartcoR Solutions
Myonex
Vial Health Technology, Inc
Information provided by (Responsible Party):
Verrica Pharmaceuticals Inc.

Brief Summary:

This is a 3-part, open-label, multicenter, dose-escalation, proof-of-concept study with a safety run-in designed to assess the safety, tolerability, MTD, and objective antitumor efficacy of ascending dose strengths of LTX 315 when administered intratumorally to adults with biopsy proven basal cell carcinoma (BCC).

The study is expected to enroll approximately 66 subjects with a histological diagnosis of BCC in at least 1 eligible target lesion (confirmed by punch or shave biopsy).


Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma Skin Cancer Cancer of the Skin, Basal Cell Cancer of the Skin Drug: LTX-315 Part 1 Drug: LTX-315 Part 2 Drug: LTX-315 Part 3 Phase 2

Detailed Description:

This is a 3-part, open-label, multicenter, dose-escalation, proof-of-concept study with a safety run-in designed to assess the safety, tolerability, maximum tolerated dose (MTD), and objective antitumor efficacy of ascending dose strengths of LTX 315 when administered intratumorally to adults with biopsy proven BCC.

The study is expected to enroll approximately 66 subjects with a histological diagnosis of BCC in at least 1 eligible target lesion (confirmed by punch or shave biopsy).

All enrolled subjects will receive LTX-315 intradermal injection on an outpatient basis into up to 2 target lesions. In all Parts of the study (1, 2, or 3, as below), each 7 day treatment week comprises up to 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing will commence in a single target lesion. Once a lesion has necrosed, treatment of that lesion stops, and treatment of subsequent target lesions (up to 2 total) may continue on Day 1 of the following week.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is an open-label, multicenter, dose-escalating study. Eligible subjects will be enrolled sequentially.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label, Proof-of-concept Study With Safety Run in to Evaluate the Safety, Pharmacokinetics, and Efficacy of LTX-315 in Adult Subjects With Basal Cell Carcinoma
Actual Study Start Date : February 1, 2022
Estimated Primary Completion Date : September 29, 2023
Estimated Study Completion Date : September 29, 2023

Arm Intervention/treatment
Experimental: Part 1 LTX-315 Safety Run-in
In Part 1 of the trial, the starting total daily dose for the evaluation of LTX-315 will be 2 mg for the first subject. Subjects will receive ascending once daily doses (increasing in 1 mg increments for up to 3 days in a 7 day treatment week [≥4 days off between treatment weeks]) until the first lesion is necrosed or until the subject experiences a DLT, whichever occurs first.
Drug: LTX-315 Part 1
LTX-315 once-daily dosing; starting total daily dose of 2 mg for the first subject. Ascending once-daily 1 mg dosing increments (eg, 2 mg on Day 1, 3 mg on Day 2). Subjects may be treated for a maximum of 2 weeks and a maximum total daily dose of 8 mg in Part 1. The starting dose will be escalated between subject cohorts in 1-mg increments after the previous cohort has completed Week 1 dosing (the DLT observation period).

Experimental: Part 2 LTX-315 Safety Run-in
Part 2 will be initiated upon completion of Part 1 to confirm the MTD. One subject will be enrolled to receive treatment at the preliminary MTD (ie, the dose below which any DLTs occurred on Part 1). The planned dosing regimen in Week 1 of Part 2 will be an LTX 315 loading dose on Week 1/Day 1 (W1D1) at half the target dose, followed by total daily doses at the full target dose for the remaining dosing days of the treatment week (up to 3) until the lesion is necrosed
Drug: LTX-315 Part 2
LTX-315 once-daily dosing; starting dose is the preliminary MTD (ie, the dose below which any DLTs occurred in Part 1). Week 1 Day 1 (W1D1) loading dose of half the target dose; remaining 2 doses in the first treatment week (up to 3 consecutive daily doses) will be the full target dose without a loading dose. Only W1D1 for each subject will have a loading dose (ie, no loading doses in any remaining doses), and subjects may be treated for a maximum of 2 weeks at the same dose. Dose will be escalated between subject cohorts in 1 mg increments after the previous cohort has completed Week 1 dosing (the DLT observation period).

Experimental: Part 3 LTX-315 Dose Expansion
Part 3 will be initiated with 2 dose cohorts of up to 20 subjects each that will be enrolled to receive LTX 315 at the confirmed MTD and the dose immediately below the MTD. Alternatively, the Safety Review Committee (SRC) may designate a lower dose for exploration of efficacy based on the results of Part 2. Subjects will receive LTX-315 until the target lesion is necrosed. Doses will be administered daily in accordance with the dosing regimen determined in Part 2.
Drug: LTX-315 Part 3
LTX-315 once-daily dosing initiated with 2 dose cohorts: Cohort 1 will receive LTX-315 at the confirmed MTD; Cohort 2 will receive LTX-315 at the dose immediately below the MTD. Subjects may be treated for a maximum of 2 weeks.




Primary Outcome Measures :
  1. Part 1: Percentage of subjects with discontinuations due to adverse events [ Time Frame: Up to 9 weeks ]
    Subjects who discontinued the study due to adverse event

  2. Part 1: Percentage of subjects with dose-limiting toxicities (DLTs) [ Time Frame: Day 4 (Safety Assessment) ]
    Subjects with pre-determined dose-limiting toxicities such as hypotension (specific criteria); significant elevation of serum tryptase; Grade 2 or higher adverse event (with specific criteria)

  3. Part 1: Percentage of subjects with Cutaneous Reaction by severity [ Time Frame: Up to 9 weeks ]
    Evaluation of the tissue condition at the treatment site for the presence and severity of each of the following cutaneous reactions; Erythema, Induration, Swelling, Blister Formation, Desquamation, Erosion, Ulceration, Necrosis by a scale of None; Mild; Moderate; Severe.

  4. Part 2: Percent of subjects with adverse events [ Time Frame: Up to 9 weeks ]
    Subject with adverse events

  5. Part 2: Percentage of subjects with discontinuations due to adverse events [ Time Frame: Up to 9 weeks ]
    Subjects that discontinued study due to adverse events

  6. Part 2: Percent of subjects with dose-limiting toxicities (DLTs) [ Time Frame: Day 4 (Safety Assessment) ]
    Subjects with pre-determined dose-limiting toxicities such as hypotension (specific criteria); significant elevation of serum tryptase; Grade 2 or higher adverse event (with specific criteria)

  7. Part 2: Percentage of subjects with Cutaneous Reaction by severity [ Time Frame: Up to 42 days ]
    Evaluation of the tissue condition at the treatment site for the presence and severity of each of the following cutaneous reactions; Erythema, Induration, Swelling, Blister Formation, Desquamation, Erosion, Ulceration, Necrosis by a scale of None; Mild; Moderate; Severe.

  8. Part 3: Percentage of subjects with complete response at excision [ Time Frame: Day 28 ]
    Percentage of subjects with both clinical and histological clearance of treated lesion(s)


Secondary Outcome Measures :
  1. Part 2: Percentage of subjects with histological clearance of treated lesion(s) at excision [ Time Frame: Day 28 ]
    Subjects with histological clearance of treated lesion(s) at excision

  2. Part 3: Percent of subjects with adverse events [ Time Frame: Up to 9 weeks ]
    Subjects with treatment-related adverse events; treatment-related serious adverse events

  3. Part 3: Percentage of subjects with Cutaneous Reaction by severity [ Time Frame: Up to 42 days ]
    Evaluation of the tissue condition at the treatment site for the presence and severity of each of the following cutaneous reactions; Erythema, Induration, Swelling, Blister Formation, Desquamation, Erosion, Ulceration, Necrosis by a scale of None; Mild; Moderate; Severe.

  4. Part 3: Percentage of subjects with histological clearance of treated lesion(s) at excision [ Time Frame: Day 28 ]
    Subjects with histological clearance of treated lesion(s) at excision

  5. Part 3: Percentage of subjects with clinical clearance of treated lesion(s) at excision [ Time Frame: Day 28 ]
    Clinical clearance of treated lesion at excision as determined by visual assessment (no residual tumor seen on visual inspection)

  6. Part 3: Percentage of subjects with abscopal effect at excision [ Time Frame: Day 28 ]
    Abscopal effect as determined by clinical and histological clearance of nontreated lesions at excision

  7. Part 3: Mean estimated remaining tumor volume at excision [ Time Frame: Day 28 ]
    Estimate of remaining tumor volume (necrotic cells:tumor cells) at excision

  8. Part 3: Percent of subjects with Physician's Global Assessment by scale [ Time Frame: Up to 42 days ]
    Physician's global assessment of improvement per lesion as measured by the following scale: 100% improvement, no visible tumor; 75% to <100% improvement; 50% to <75% improvement; 25% to <50% improvement; up to 25% improvement; no change; worse



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. Adults ≥18 years of age
  2. Clinically suspected BCC with at least 1 and up to 5 eligible lesion(s) suitable for biopsy and excision (see Section 5.4)
  3. Willing to refrain from using nonapproved topical agents on, or within 2 cm of, the target BCC lesions and surrounding areas during the treatment period. Subjects should use topical agents that are gentle (eg, Aquaphor, CeraVe) and will not irritate the skin in these areas.
  4. Willing to refrain from exposure to direct sunlight or ultraviolet light and to avoid the use of tanning parlors for the duration of the study
  5. Written informed consent obtained, including consent for tissue to be examined by the central dermatopathologist and stored by the Sponsor or designee
  6. Willing to undergo BCC surgical excision procedure of target and nontarget BCC lesions after study treatment
  7. Willing to delay surgical excision of target and nontarget BCC lesions until the end of treatment (EOT) visit
  8. Provides written consent to allow photographs of the target and nontarget BCC lesion to be used as part of the study data
  9. Willing to practice a highly effective method of birth control while on study and until 4 weeks after the last treatment. Highly effective birth control includes sexual abstinence, vasectomy, bilateral tubal ligation/occlusion, or a condom with spermicide (men) combined with hormonal birth control or intrauterine device in women.

BCC Lesion Inclusion Criterion

  1. For punch biopsies: the size of the lesion(s) must be ≥0.5 cm and </=2 cm in the longest diameter prior to punch biopsy.
  2. Histological diagnosis of nodular, micronodular, or superficial BCC, as confirmed by punch or shave biopsy performed within 28 days of W1D1. (NOTE: HISTORICAL punch or shave biopsies are acceptable, provided that the biopsy was performed according to clinical standard of care and was collected within the 28 days prior to Screening.)

Exclusion Criteria:

  1. Presence of known or suspected systemic cancer
  2. Treatment with systemic chemotherapeutic agents within the 6 months prior to the screening visit
  3. Treatment with systemic immunotherapy, immunomodulators or immunosuppressants within the 12 weeks prior to the screening period
  4. Genetic or nevoid conditions (eg, Gorlin / basal cell nevus syndrome, xeroderma pigmentosa)
  5. Clinically significant laboratory values, as assessed by the investigator, for the tests listed in the Schedule of Assessments, including:

    1. serum creatinine >1.5× the upper limits of normal and
    2. serum tryptase concentration >11.4 ng/mL
  6. Chronic medical condition that in the judgment of the investigator(s) would interfere with the performance of the study or would place the subject at undue risk, such as, but not limited to:

    1. Uncontrolled infection or infection requiring antibiotics
    2. Uncontrolled cardiac failure: Classification III or IV New York Heart Association
    3. History of cerebrovascular or cardiac disorders, or subjects at particular risk of sequelae following a short hypotensive episode, including subjects with systolic BP <100 mmHg and/or diastolic BP <60 mmHg at screening or Day 1
    4. Uncontrolled systemic or gastrointestinal inflammatory conditions
    5. Known bone marrow dysplasia
    6. History of positive tests for human immunodeficiency virus/acquired immunodeficiency syndrome or active hepatitis B or C
    7. History of systemic autoimmune disease requiring anti-inflammatory or immunosuppressive therapy within 3 months prior to Day 1, with the following exceptions:

    i. Subjects with a history of autoimmune thyroiditis are eligible provided the subject requires only thyroid hormone replacement therapy and disease has been stable for ≥1 year

    ii. Subjects with well-controlled type I diabetes (in the opinion of the investigator) are eligible

    h. Known mast cell activation syndrome, mastocytosis, or chronic idiopathic urticaria

  7. Known sensitivity to any of the ingredients in the study medication
  8. Elective surgery within 4 weeks prior to the screening visit, during the study, or 4 weeks after the treatment period
  9. Evidence of current chronic alcohol or drug abuse
  10. Current enrollment in an investigational drug or device study or participation in such a study within 4 weeks of the screening visit
  11. In the investigator's opinion, evidence of unwillingness, or inability to follow the restrictions of the protocol and complete the study
  12. Females who are pregnant or breastfeeding

BCC Lesion Exclusion Criteria

  1. Recurrent or previously treated lesions
  2. Lesions within 1 cm of the eyelids or lips, or on the hands, feet, ears, nose, and genitalia
  3. Histological evidence of any other tumor in the biopsy specimen
  4. Histological evidence of infiltrative, desmoplastic, sclerosing, or morpheaform BCC subtypes in the biopsy specimen
  5. Medium- and high-risk basal cell carcinomas as defined by the National Comprehensive Cancer Network (NCCN) or Mohs Appropriate Use Criteria (ie, BCCs eligible for Mohs surgery).

    TARGET LESION EXCLUSION ONLY:

  6. For subjects with severe stasis dermatitis, target BCC lesions may not be on the lower extremities
  7. Within 2 cm of the target BCC lesion(s):

    1. Treatment with the following topical agents within the 12 weeks prior to the screening visit: aminolevulinic acid, 5-fluorouracil, corticosteroids, diclofenac, imiquimod, ingenol mebutate
    2. Treatment with surgical excision, or curettage within the 2 weeks prior to the screening visit
    3. Evidence of dermatological disease or confounding skin condition that may interfere with clinical evaluation (ie, psoriasis, atopic dermatitis, eczema, propensity to form keloids or hypertrophic scarring)
    4. Use of topical immunomodulators during study
  8. Within 5 cm of the target BCC lesion(s): history of any skin cancer, except for other currently identified target and nontarget BCC lesions
  9. Target BCC lesion is in the area of prior resurfacing procedure with CO2 laser or any photodynamic and phototherapy treatment within the 3 months prior to the screening visit

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): NCT05188729


Contacts
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Contact: Betsey Zbyszynski 619-865-8562 betsey@vial.com

Locations
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United States, California
Therapeutics Clinical Research Recruiting
San Diego, California, United States, 92123
Contact    858-571-6800      
Principal Investigator: Neal D Bhatia, MD         
United States, Florida
Florida Center for Dermatology Recruiting
Saint Augustine, Florida, United States, 32080
Contact       research@fcderm.com   
Principal Investigator: Jonathan Kantor, MD         
United States, Maryland
Lawrence J Green, MD LLC Recruiting
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
Verrica Pharmaceuticals Inc.
Instat Clinical Research
HeartcoR Solutions
Myonex
Vial Health Technology, Inc
Investigators
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Principal Investigator: Neal Bhatia, MD Therapeutics Clinical Research
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Responsible Party: Verrica Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT05188729    
Other Study ID Numbers: VP-LTX-315-201
First Posted: January 12, 2022    Key Record Dates
Last Update Posted: September 15, 2022
Last Verified: September 2022
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
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Basal Cell
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell
Neoplasms by Site
Skin Diseases