A Study of ASP1012 in Adults With Solid Tumors

NCT06171178 | Terminated Phase 1 FDA Drug

• 1 other identifier: 1012-CL-0101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

Brief Summary

ASP1012 is a type of virus called an oncolytic virus which is used to treat some cancers. ASP1012 was changed in a laboratory to infect and kill cancer cells, leaving healthy cells alone. It also makes the cancer cells visible to the immune system which will fight the cancer cells. Before ASP1012 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This will help find a suitable dose for future studies and check for potential medical problems from the treatment. In this study, ASP1012 is being tested in humans for the first time. ASP1012 has already been tested in the laboratory and in animals. This is the standard way new potential treatments are developed. People in this study will be adults whose tumor has either grown outside of the area where it started (locally advanced) or it has spread to other parts of the body (metastatic). They will receive ASP1012. Also, some people will receive ASP1012 with pembrolizumab, an approved medicine. There are 2 main aims of this study. The first is to learn if people with certain solid tumors can tolerate different doses of ASP1012. The second is to find a suitable dose of ASP1012. This study will be in 3 parts. Part 1 is called Dose Escalation. People with locally advanced or metastatic tumors can take part. They will have been previously treated with all available standard cancer therapies. Different small groups of people will receive lower to higher doses of ASP1012. For each dose, any medical problems will be recorded. This will help to find suitable doses of ASP1012 to use in Parts 2 and 3 of the study. The first group will receive the lowest dose of ASP1012. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP1012. The panel will do this for each group until all groups have taken ASP1012 or until suitable doses have been selected for Parts 2 and 3. Part 2 is called Dose Expansion. 3 groups will take part: people with previously-treated melanoma (a type of skin cancer) that have not responded to their treatment (refractory) or their cancer has come back (relapsed), people with newly-diagnosed or untreated melanoma, and people with previously-treated solid tumors. People with previously-treated melanoma will receive ASP1012 at the dose worked out from Part 1. People with previously-treated solid tumors will receive ASP1012 with pembrolizumab. The first few people will receive ASP1012 at a lower dose than the dose worked out from Part 1, to check the safety of the treatments being given together. If there are no safety issues: the next people in the solid tumor group will receive ASP1012 at the dose worked out from Part 1, with pembrolizumab; also people with untreated melanoma will receive ASP1012 at the dose worked out from Part 1, with pembrolizumab. Part 3 is also a Dose Expansion for people with other specific cancers. These are stomach cancer, ovarian cancer, or colorectal cancer. If people with certain tumors respond well in Parts 1 and 2 of the study, other people with this same type of tumor can also take part in Part 3. For all parts of the study, ASP1012 will be given through a vein. This is called an infusion. Each treatment cycle is 21 days long. People will start with 3 treatment cycles. People in the study may receive extra treatment cycles, if they respond well to treatment. People with melanoma who are receiving ASP1012 with pembrolizumab will not be offered the extra treatment cycles. People can stop leave the study early if: they have medical problems from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come back for treatment. People will visit the clinic on certain days during their treatment. Some visits will be virtual or by phone. During all clinic visits, the study doctors will check for any medical problems from ASP1012. They will also check vital signs. Vital signs include temperature, pulse, breathing rate, the amount of oxygen in the blood, and blood pressure. At some visits, other checks will also include a medical examination, and an electrocardiogram (ECG) to check the heart rhythm, blood draws and urine samples for testing. A tumor sample, if available, will be taken during the first treatment cycle. People will have imaging scans and have blood draws for testing every 6 weeks during and after treatment. This will stop if they leave the study early. People will visit the clinic within 7 days and 30 days after stopping treatment. At both visits, the study doctors will check for any medical problems from ASP1012. Other checks will include a medical examination, blood draws and urine samples for testing and checking vital signs. An ECG will also be done at the 7-day visit. After the 30-day visit, clinic staff will phone people in the study every 12 weeks to check the condition of their cancer for up to 1 year.

Conditions

Solid Tumor

Keywords

Locally Advanced Solid Tumors; Metastatic Solid Tumors; ASP1012; Melanoma

Outcome Measures

Primary Outcomes (6)

• Incidence of Dose Limiting Toxicities (DLTs)

  A DLT will be defined as any event meeting the DLT criteria occurring during the DLT assessment period that is considered possibly, probably or definitely related to ASP1012.

  Up to 28 days

• Number of participants with Adverse Events (AEs)

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the (study) procedures.

  Up to 19 months

• Number of participants with laboratory value abnormalities and/or AEs

  Number of participants with potentially clinically significant laboratory values.

  Up to 7 months

• Number of participants with vital sign abnormalities and/or AEs

  Number of participants with potentially clinically significant vital sign values.

  Up to 7 months

• Number of participants with electrocardiogram (ECG) abnormalities and/or AEs

  Number of participants with potentially clinically significant ECG values.

  Up to 6 months

• Number of participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores

  The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

  Up to 7 months

Secondary Outcomes (18)

• ASP1012 viral DNA in blood

  Up to 7 months

• Viral shedding of ASP1012 in urine

  Up to 7 months

• Viral shedding of ASP1012 in saliva

  Up to 7 months

• Viral shedding of ASP1012 in feces (part 1)

  Up to 6 months

• Number of participants with positive anti-drug antibodies to ASP1012

  Up to 6 months

Study Arms (8)

Part 1: ASP1012 Dose Escalation

EXPERIMENTAL

Participants with previously treated solid tumor types will receive ASP1012 in a 21-day cycle.

Drug: ASP1012

Part 2: ASP1012 Dose Expansion (Monotherapy)

EXPERIMENTAL

Participants with previously treated melanoma will receive ASP1012 with dose level(s) selected from dose escalation (Part 1) in a 21-day cycle.

Drug: ASP1012

Part 2: ASP1012 + Pembrolizumab Dose Expansion (previously treated solid tumors)

EXPERIMENTAL

Participants with previously treated solid tumors, will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.

Drug: ASP1012; Drug: Pembrolizumab

Part 2: ASP1012 + Pembrolizumab Dose Expansion (treatment-naïve melanoma)

EXPERIMENTAL

Participants with treatment-naïve melanoma will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.

Drug: ASP1012; Drug: Pembrolizumab

Part 3: ASP1012 Dose Expansion (previously treated gastric cancer)

EXPERIMENTAL

Participants with previously treated gastric cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Drug: ASP1012

Part 3: ASP1012 Dose Expansion (colorectal cancer [CRC])

EXPERIMENTAL

Participants with CRC will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Drug: ASP1012

Part 3: ASP1012 Dose Expansion (ovarian cancer)

EXPERIMENTAL

Participants with ovarian cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Drug: ASP1012

Part 3: ASP1012 Dose Expansion (other solid tumor type)

EXPERIMENTAL

Participants with other solid tumor type will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Drug: ASP1012

Interventions

ASP1012 DRUG

Intravenous (IV) infusion

Part 1: ASP1012 Dose Escalation; Part 2: ASP1012 + Pembrolizumab Dose Expansion (previously treated solid tumors); Part 2: ASP1012 + Pembrolizumab Dose Expansion (treatment-naïve melanoma); Part 2: ASP1012 Dose Expansion (Monotherapy); Part 3: ASP1012 Dose Expansion (colorectal cancer [CRC]); Part 3: ASP1012 Dose Expansion (other solid tumor type); Part 3: ASP1012 Dose Expansion (ovarian cancer); Part 3: ASP1012 Dose Expansion (previously treated gastric cancer)

Pembrolizumab DRUG

IV infusion

Part 2: ASP1012 + Pembrolizumab Dose Expansion (previously treated solid tumors); Part 2: ASP1012 + Pembrolizumab Dose Expansion (treatment-naïve melanoma)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants in Parts 1 and 2 must have histologically, or cytologically, confirmed diagnosis of locally advanced or metastatic solid tumor(s).
• Dose Escalation (Part 1) - all previously treated participants with solid tumor types
• Dose Expansion (Part 2)
• Participants with previously treated cutaneous melanoma, that is, anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) alone or in combination with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor. Participants with BRAF-mutant melanoma must have received a v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor as monotherapy or in combination with other targeted agents (for example, murine embryonic fibroblasts (MEK) inhibitors).
• Participants with previously treated solid tumors,
• Participants with stage IIIB to IIID or oligometastatic resectable stage IV, treatment-naïve melanoma that are amenable to resection.
• Note: Participants with acral lentiginous melanoma will be excluded.
• Participants in Part 3 (Dose Expansion) must have histologically, or cytologically confirmed diagnosis of either:
• Previously treated (at least 1 line of prior therapy) gastric cancer (including gastroesophageal junction cancer \[type 2 and 3 only\]). Prior lines of therapy may include combination chemotherapy such as FOLFOX based regimen containing 5-flurouracil, leucovorin and oxaliplatin, targeted therapies against human epidermal growth factor receptor 2 (HER2+) tumors and checkpoint inhibitors.
• Stage II to IV CRC in complete remission with no measurable disease as defined by RECIST v1.1 following surgical resection and adjuvant therapy with circulating tumor deoxyribonucleic acid (ctDNA) detectable by local testing; the ctDNA positivity will be confirmed during the trial by centralized testing Note: Participants with Stage IV CRC are limited to those with oligometastatic disease in liver. Participants with CRC must have received and completed standard of care and adjuvant therapies which may include fluoropyrimidine, oxaliplatin, bevacizumab, and irinotecan-based chemotherapy and surgery.
• Stage II to IV ovarian cancer including breast cancer gene mutations in complete remission with no measurable disease as defined by RECIST v1.1 following surgical resection and adjuvant therapy with CA-125 concentration exceeding 2 times of normal level (\> 70 units per milliliter \[U/mL\]) as measured by local testing. Participants with ovarian cancer must have received standard of care and adjuvant therapies which may include platinum-based chemotherapy and/or poly-ADP ribose polymerase (PARP) inhibitors.
• Other solid tumor type (when identified), for example, a tumor type in which antitumor activity or biomarker response is observed in Parts 1 or 2 or additional tumor types of interest.
• Participant has measurable disease as determined by RECIST v1.1, except for participants with CRC and ovarian cancer enrolled in Part 3. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Participant has progressed, relapsed or discontinued for toxicity during or after the last systemic anti-neoplastic therapy and is unlikely to achieve clinical benefit from standard of care therapies per investigator, except for Part 2 participants with treatment-naïve melanoma and Part 3 (participants with CRC and ovarian cancer). There is no limit to the number of prior anti-neoplastic therapies received.
• Participant has a predicted life expectancy ≥ 12 weeks.

You may not qualify if:

• Participant has ongoing toxicity ≥ Grade 2 per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 considered clinically significant and attributable to prior anti-neoplastic therapies. Note: Participants with peripheral neuropathy, type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (for example, vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
• Participant has had major surgery ≤ 4 weeks of signing the informed consent form (ICF).
• Participant has symptomatic or untreated central nervous system metastases or leptomeningeal disease. Participants with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to screening) and off steroids for at least 2 weeks prior to first administration of ASP1012.
• Participant has active or prior autoimmune or inflammatory disorders requiring systemic therapy within the past 2 years (including inflammatory skin conditions, or inflammatory bowel disease \[for example, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, systemic lupus erythematosus, non-infectious pneumonitis, Sarcoidosis syndrome, Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:
• Participant with type 1 diabetes mellitus
• Participant with vitiligo or alopecia
• Participant with endocrinopathies stably maintained on appropriate replacement therapy.
• Participant with any chronic skin condition that does not require systemic therapy
• Participant with eczema or history of eczema requiring systemic treatment.
• Participant with another malignancy that currently requires treatment
• Participant with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of ASP1012. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Participant has received a prior allogeneic bone marrow or solid organ transplant.
• Participant has a condition requiring use of anti-viral agents with a potential to inhibit vaccinia replication. Prophylactic use of anti-viral agents (e.g., acyclovir) is permitted.
• Participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, any form of substance abuse or psychiatric illness/social situations that would limit compliance with study visits or requirements or a condition that could invalidate communication.
• Participant has a known history of human immunodeficiency virus (HIV) infection or suffers from other acquired and congenital immunodeficiency diseases. HIV testing is not required for the purposes of this study unless mandated by local health authority.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (8)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals

Iowa City, Iowa, 52242, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Central Contact

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 14, 2023
• Study Start: May 15, 2024
• Primary Completion: September 10, 2025
• Study Completion: September 10, 2025
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (8)