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

Phase 2

Completed

• Conditions: Carcinoma; Cancer of the Skin; Basal Cell Carcinoma; Skin Cancer; Cancer of the Skin, Basal Cell

• Registration Number: NCT05188729
• Lead Sponsor: Verrica Pharmaceuticals Inc.

Brief Summary

This is a 2-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 VP-315 when administered intratumorally to adults with biopsy proven basal cell carcinoma (BCC).

The study is expected to enroll approximately 86 subjects with a histological diagnosis of BCC in at least 1 eligible target lesion (confirmed by punch or shave biopsy).

Detailed Description

This is a 2-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 VP-315 when administered intratumorally to adults with biopsy proven BCC.

The study is expected to enroll approximately 86 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 VP-315 intradermal injection on an outpatient basis into up to 2 target lesions. In all Parts of the study (1 or 2, 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 is observed to be fully necrotic (Part 1, Part 2; Cohorts 1-2 only), treatment of that lesion stops, and treatment of subsequent target lesions (up to 2 total) may continue on Day 1 of the following week. In Part 2, Cohorts 4 and 5, treatment of a second target lesion begins on W2D1 (not based on status of necrosis of target lesion 1).

Study Timeline

• Study First Submitted: 2021-12-13
• Study First Submitted QC: 2022-01-06
• Study First Posted: 2022-01-12
• Study Start: 2022-02-01
• Primary Completion: 2024-04-15
• Study Completion: 2024-04-15
• Results First Submitted: 2025-04-15
• Status Verified: 2025-05
• Results First Submitted QC: 2025-06-16
• Last Update Submitted: 2025-06-16
• Results First Posted: 2025-06-18
• Last Update Posted: 2025-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

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
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 Eligibility

Eligible lesions are those that meet the BCC lesion eligibility specifications described herein, from samples that are either from:

• HISTORICAL punch or shave biopsies (i.e., samples collected according to clinical standard of care collected within the 90 days prior to W1D1);
• A 2-mm punch biopsy collected within 90 days of W1D1 for suspected BCC ≥0.5 cm to 1.0 cm, and 3-mm punch biopsy for suspected BCC >1.0 cm to 2.0 cm; or
• A shave biopsy performed according to standard of care to include superficial or middle papillary dermis collected within 90 days of W1D1.

Lesions must meet the following criteria to be eligible for treatment

BCC Lesion Inclusion Criteria

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 90 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 90 days prior to Screening.) Subject Exclusion Criteria Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

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 pigmentosum)

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. Subjects presenting with a systolic BP <110 mmHg and/or diastolic BP <70 mmHg at Screening or Week 1 Day 1 or a history of cerebrovascular or cardiac disorders, or subjects at particular risk of sequelae following a short hypotensive episode.
   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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Part 1: Percentage of Subjects With Discontinuations Due to Adverse Events	Up to 9 weeks	Part 1: Percentage of subjects that discontinued the study due to adverse event
Part 1: Percentage of Subjects With Dose-limiting Toxicities (DLTs)	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)
Part 1: Percentage of Subjects With Cutaneous Reaction by Maximum Severity	Up to 9 weeks	Cutaneous injection site reactions are defined as the following preferred terms: Injection site erythema, Injection site induration, Injection site swelling, Injection site vesicles, Injection site exfoliation, Injection site erosion, Injection site ulcer, Injection site necrosis.; The intended scale for cutaneous injection site reactions is mild, moderate, severe from CRA.; Subjects having more than one event may appear in more than one System Organ Class or Preferred Term but are counted at most once per each SOC and PT at the maximum severity.; Cutaneous injection site reactions are types of reactions that can be expected to occur.
Part 2: Percent of Subjects With Adverse Events	Up to 15 weeks	Part 2: Percent of subjects with adverse events, treatment-related AEs
Part 2: Percent of Subjects With Treatment Related Adverse Events of Special Interest (TRAEs SI)	Treatment Days up to 2 weeks	Subjects with pre-determined TRAEs of SI such as hypotension (specific criteria); significant elevation of serum tryptase; Grade 2 or higher adverse event (with specific criteria)
Part 2: Percentage of Subjects With Cutaneous Reaction by Maximum Severity	Up to 105 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. Subjects having more than one event may appear in more than one SOC or PT but are counted at most once per each SOC and PT at the maximum severity.; Cutaneous injection site reactions are types of reactions that can be expected to occur. The intended scale for cutaneous injection site reactions is mild, moderate, severe from CRA
Part 2: Percentage of Subjects With Study Discontinuations Due to Adverse Events	Up to 15 weeks	Part 2: Percentage of subjects with study discontinuations due to adverse events.

Secondary Outcome Measures

Name	Time	Method
Part 2: Percentage of Subjects With Clinical Clearance of Treated Lesion(s) at Excision	Day 84-91	Clinical clearance of Target Lesion at excision as determined by visual assessment (no residual tumor seen on visual inspection). Clinical assessment using Physician Global Assessment (PGA). PGA scale: 100% Improvement, no visible tumor; 75% to less than 100% improvement, 50% to less than 75% improvement, 25% to less than 50% improvement, Up to 25% improvement, No change, Worse.
Part 2: Percentage of Subjects With Histological Clearance of Treated Lesion(s) at Excision	Day 84-91	Percentage of Subjects with histological clearance of treated lesion(s) at excision. Histologic clearance confirmed by central dermatopathologist.; Percentage is calculated using the number of subjects with non-missing responses within lesion as the denominator.; \*Scar indicates complete histologic clearance
Part 2: Mean Estimated Remaining Tumor Volume at Excision	Day 84-91	Estimate of remaining tumor volume (necrotic cells:tumor cells) at excision by central dermatopathologist; Scale: 0 = None Remaining to 100 = All Remaining.
Part 2 (Cohorts 4 and 5 Expansion Groups): Plasma Concentrations of VP-315	Day 1-2	Pharmacokinetics (PK) of an 8 mg dose of VP-315 administered with the optimal dosing regimen

Trial Locations

Locations (13)

ClearlyDerm; 🇺🇸 Boca Raton, Florida, United States

Life Clinical Trials; 🇺🇸 Coral Springs, Florida, United States

Affinity Health; 🇺🇸 Oakbrook Terrace, Illinois, United States

DermAssociates; 🇺🇸 Rockville, Maryland, United States

ActivMed Research - Borthwick; 🇺🇸 Portsmouth, New Hampshire, United States

UPMC St. Margaret; 🇺🇸 Pittsburgh, Pennsylvania, United States

Austin Institute of Clinical Research - Houston; 🇺🇸 Houston, Texas, United States

Therapeutics Clinical Research; 🇺🇸 San Diego, California, United States

Florida Center for Dermatology; 🇺🇸 Saint Augustine, Florida, United States

Gwinnett Dermatology; 🇺🇸 Snellville, Georgia, United States

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