A Study of DSP-7888 Dosing Emulsion in Adult Patients With Advanced Malignancies

NCT02498665 | Completed Phase 1

• 1 other identifier: BBI-DSP7888-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multicenter, open label, Phase 1 dose-escalation study of DSP-7888 Dosing Emulsion administered to adult patients with advanced malignancies. Patients will be administered escalating doses of DSP-7888 Dosing Emulsion intradermally or subcutaneously in accordance with the following regimen: once weekly for four weeks during the Induction Phase, once every 7 to 14 days for 6 weeks during the Consolidation Phase, and once every 14 to 28 days until a discontinuation criterion is met during the Maintenance Phase. Once RP2D is determined from either the intradermal or subcutaneous group, an additional 40 patients evaluable for response may be enrolled as an expansion cohort at this dose and route of administration to confirm safety and tolerability. Separate from the dose-ascending cohort and RP2D expansion cohort described previously, and once the intradermal dose-ascending cohort is completed, up to 20 MDS patients who are refractory to treatment with hypomethylating agents (HMAs) will be enrolled into an MDS expansion cohort. Of these 20 MDS patients, one-half will receive DSP-7888 at 10.5 mg according to the modified schedule employed in Phase 1 (every week for 4 weeks, every 2 weeks until Week 24, and then every 4 weeks; \[MDS Cohort 1\]). The other half of the MDS patients will receive DSP-7888 at 10.5 mg in an alternative dosing schedule where DSP-7888 is administered every 2 weeks until Week 24, after which it will be administered every 4 weeks (MDS Cohort 2).

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Glioblastoma Multiforme; Melanoma; Non-Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Sarcoma; Renal Cell Carcinoma

Keywords

Wilms' Tumor 1; Vaccine; Neoplasms

Outcome Measures

Primary Outcomes (3)

• Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing dose-limiting toxicities (DLTs)

  4 weeks

• Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing duration of study treatment

  12 months

• Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs)

  4 weeks

Secondary Outcomes (3)

• Assessment of the preliminary anti-tumor activity by assessing Progression-Free Survival (solid tumors and acute myeloid leukemia (AML))

  12 months

• Overall Survival

  12 months

• Pharmacodynamic activity of DSP-7888 Dosing Emulsion as assessed by biomarker analysis

  12 months

Study Arms (3)

Dosing Escalation Cohort

EXPERIMENTAL

Patients will be administered escalating doses of DSP-7888 Dosing Emulsion intradermally or subcutaneously. Dose-escalation will proceed according to the Criteria for Dose Escalation and Criteria for Determination of Dose-Limiting Toxicity (DLT) as indicated below. Dose Level I: 3.5 mg, Dose Level II: 10.5 mg, Dose Level III: 17.5 mg

Drug: DSP-7888 Dosing Emulsion

MDS Cohort 1

EXPERIMENTAL

Patients will be intradermally administered of DSP-7888 at 10.5 mg every week for 4 weeks, every 2 weeks until Week 24, and then every 4 weeks.

Drug: DSP-7888 Dosing Emulsion

MDS Cohort 2

EXPERIMENTAL

Patients will be intradermally administered of DSP-7888 at 10.5 mg every 2 weeks until Week 24, and then every 4 weeks.

Drug: DSP-7888 Dosing Emulsion

Interventions

DSP-7888 Dosing Emulsion DRUG

Dose escalation cohort: Patients will be administered escalating doses of DSP-7888 Dosing Emulsion intradermally or subcutaneously in accordance with the following regimen: once weekly for four weeks during the Induction Phase, once every 7 to 14 days for 6 weeks during the Consolidation Phase, and once every 14 to 28 days until a discontinuation criterion is met during the Maintenance Phase. MDS cohort 1: Patients will be intradermally administered of DSP-7888 at 10.5 mg every week for 4 weeks, every 2 weeks until Week 24, and then every 4 weeks. MDS cohort 2: Patients will be intradermally administered of DSP-7888 at 10.5 mg every 2 weeks until Week 24, and then every 4 weeks.

Also known as: adegramotide and nelatimotide

Dosing Escalation Cohort; MDS Cohort 1; MDS Cohort 2

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements
• Patient has one of the following histologically or cytologically confirmed advanced malignancies: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), glioblastoma multiforme (GBM), melanoma, non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, sarcoma, renal cell carcinoma (RCC)
• Patient must meet at least one of the following criteria: a. Progressed or recurrent despite standard therapy, b. No standard therapy exists for this malignancy, c. Patient is intolerant of standard therapy, d. Patient is not a candidate for standard therapy, e. For AML and MDS patients: patient is not a candidate for allogeneic hematopoietic stem cell transplantation, f, For sarcoma patients: f-1. Patient has disease that is metastatic or unresectable, f-2. Patient with metastatic disease has had at least one prior line of therapy for metastatic disease, f-3. No curative multimodality options exist
• Patients must be positive for at least one of the following human leukocyte antigens (HLA): a. HLA-A\*02:01, b. HLA-A\*02:06, c. HLA-A\*24:02
• ≥ 18 years of age
• For patients with solid tumors, one of the following must apply: a. Patient has measurable disease as defined by the immune-related response criteria (irRC), b. Patient has ovarian cancer and has disease evaluable by CA-125 only
• For patients with solid tumors, the following criteria apply: a. Hemoglobin ≥ 9.0 g/dl, b. Absolute lymphocyte count ≥ 1.0 x 10\^9/L, c. Absolute neutrophil count ≥ 1.5 x 10\^9/L, d. Platelets ≥ 100.0 x 10\^9/L
• Patients with MDS must have been diagnosed as MDS by WHO (4th edition) or French-American-British (FAB) classification
• Patients with MDS must have failed to respond to, or progressed after, adequate treatment with a hypomethylating agent (HMA), or had documented intolerance of an HMA, and must have an International Prognostic Scoring System (IPSS) score ≥ 1.5
• For patients with AML or MDS, patient must have white blood cell count (WBC) ≤ 50,000/mL. Hydroxyurea is allowed to achieve this change but must be discontinued a minimum of five (5) days prior to baseline evaluation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 180 days after the DSP-7888 Dosing Emulsion dose
• Females of childbearing potential must have a negative serum pregnancy test
• Total bilirubin of ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's syndrome)
• Aspartate Aminotransferase (AST) ≤ 3.0x the upper limit of normal (ULN)

You may not qualify if:

• Patient has an extensively disseminated primary glioblastoma
• Patient has acute promyelocytic leukemia (APML)
• For AML and MDS patients: patients with a dry tap on bone marrow aspiration during screening
• Patient has symptomatic brain metastases (i.e., metastases that are accompanied by neurological symptoms or that require treatment with corticosteroids)
• Patient has an infection requiring treatment with systemic antibiotics or antiviral medication or has completed treatment for such an infection within 14 days prior to planned first dose of study drug
• Patient requires systemic, pharmacologic doses of corticosteroids (equivalent to \>30 mg hydrocortisone/day) Note: Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed
• Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, human immunodeficiency virus HIV-1 or HIV-2 antibody, or has a history of a positive result for hepatitis C virus (HCV) or HIV
• Patient has received any of the following treatments within the specified timeframes: a. Surgery, radiotherapy, chemotherapy (including molecular-targeted drugs): 4 weeks (28 days), b. Immunosuppressants or cytokine formulations (excluding G-CSF): 4 weeks (28 days), c. Endocrine therapy or immunotherapy (including biological response modifier therapy): 2 weeks (14 days)
• Patient has an unresolved ≥ Grade 2 adverse event (AE) from a previous antineoplastic treatment, excluding alopecia and phlebitis
• Patient has had surgery within 4 weeks prior to first dose
• Woman who is pregnant or lactating or has a positive pregnancy test at screening. If a woman has a positive pregnancy test, further evaluation may be conducted to rule out ongoing pregnancy to allow the patient to be eligible
• Patient has any concurrent autoimmune disease or has a history of chronic or recurrent autoimmune disease; these include but are not limited to: multiple sclerosis, Grave's disease, vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, myasthenia gravis, ankylosing spondylitis, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, psoriasis requiring systemic therapy, pemphigus, temporal arteritis, dermatomyositis, Sjögren's syndrome, Goodpasture's syndrome, interstitial pneumonitis, interstitial nephritis, or Henoch-Schönlein purpura
• Patient has, in the opinion of the treating investigator, any intercurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results; these conditions include, but not limited to: congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior 6 months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than 2 medications for adequate control, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months
• Patient has Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.0 grade ≥ 2 hemorrhage
• Patient has pleural effusion, ascites, or pericardial fluid requiring drainage Note: Patient who had drain removal ≥ 14 days prior to planned first dose of study drug and has no sign of worsening is eligible

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (8)

USOR - Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

Location

USOR - TX Oncology Austin

Austin, Texas, 78705, United States

Location

USOR -TX Oncology Dallas

Dallas, Texas, 75246, United States

Location

USOR - TX Oncology Tyler

Tyler, Texas, 75702, United States

Location

USOR - VA Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

USOR - VA Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related Publications (1)

• Spira A, Hansen AR, Harb WA, Curtis KK, Koga-Yamakawa E, Origuchi M, Li Z, Ertik B, Shaib WL. Multicenter, Open-Label, Phase I Study of DSP-7888 Dosing Emulsion in Patients with Advanced Malignancies. Target Oncol. 2021 Jul;16(4):461-469. doi: 10.1007/s11523-021-00813-6. Epub 2021 May 3.

  PMID: 33939067 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Glioblastoma; Melanoma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Pancreatic Neoplasms; Sarcoma; Carcinoma, Renal Cell; Wilms Tumor; Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Neoplasms, Connective and Soft Tissue; Adenocarcinoma; Carcinoma; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

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

Study Record Dates

• First Submitted: July 13, 2015
• First Posted: July 15, 2015
• Study Start: November 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: September 1, 2018
• Last Updated: November 14, 2023

Record last verified: 2023-11

Locations

US (8)