A Study of DSP-7888 Dosing Emulsion in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Solid Tumors

NCT03311334 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BBI-DSP7888-102CI
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 19

Brief Summary

This is a Phase 1b/2, open-label, multicenter study of DSP-7888 Dosing Emulsion in combination with checkpoint inhibitors (nivolumab or pembrolizumab) in adult patients with solid tumors, that consists of 2 parts: dose search part of the study (Phase 1b and Phase 1b Enrichment Cohort) and the dose expansion part of the study (Phase 2). In Phase 1b of this study there will be 2 arms: Arm 1 and Arm 2. In Arm 1, there will be 6 to 12 patients who will be dosed with DSP-7888 Dosing Emulsion and nivolumab and in Arm 2 there will be 6 to 12 patients who will be dosed with DSP-7888 Dosing Emulsion and pembrolizumab. In addition, an enrichment cohort of a further 10 patients who have locally advanced or metastatic Renal Cell Carcinoma or Urothelial Cancer with primary or acquired resistance to previous checkpoint inhibitors will be enrolled into Phase 1b of the study to help evaluate the preliminary antitumor activity of DSP-7888 Dosing Emulsion at the safe dose level identified in the dose-search part of the study, and will be dosed with DSP-7888 Dosing Emulsion and nivolumab, or DSP-7888 Dosing Emulsion and pembrolizumab, as per the investigator's preference. At the safe, recommended dose determined in Phase 1b, platinum-resistant ovarian cancer (PROC) patients will be enrolled in Phase 2 of the study with DSP-7888 Dosing Emulsion, exploring the combination with pembrolizumab (Arm 2). In Phase 2, approximately 40 patients with PROC will be initially enrolled; additional patients may be enrolled to further assess anti-tumor activities, but the total sample size will not exceed 60 patients. This brings the total maximum study population to approximately 84 patients.

Conditions

Renal Cell Carcinoma (RCC); Urothelial Carcinoma; Primary Peritoneal Cancer; Platinum-resistant Ovarian Cancer (PROC); Serous Epithelial Ovarian Cancer; Fallopian Tube Cancer

Keywords

DSP-7888; Nelatimotide; Adegramotide; immune checkpoint inhibitor; cancer vaccine; WT1; ICI; Wilms Tumor 1; Ombipepimut-S; nivolumab; Opdivo; pembrolizumab; Keytruda; Ovarian cancer; Platinum-resistant ovarian cancer; PROC; Serous epithelial ovarian cancer; High-grade serous epithelial ovarian cancer; HGSOC; Fallopian tube cancer; FTC; Peritoneal cancer; Primary peritoneal cancer; PPC; Renal cell carcinoma; Kidney cancer; RCC; Metastatic Renal Cell Carcinoma; Metastatic RCC; Metastatic kidney cancer; Advanced Renal Cell Carcinoma; Advanced RCC; Advanced kidney cancer; Urothelial carcinoma; Bladder cancer; Transitional cell carcinoma; UC; Metastatic urothelial carcinoma; Metastatic transitional cell carcinoma; Metastatic UC; Advanced urothelial carcinoma; Advanced UC; Advanced transitional cell carcinoma

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Adverse Events and Serious Adverse Events

  From the date of signing informed consent until 30 days after last dose for an average of 3 months.

• Determination of the Recommended Phase 2 Dose (RP2D) by Assessing Dose-limiting Toxicities (DLTs).

  The RP2D was based on the data collected during phase 1b.

  28 days

• Phase II: The Objective Response Rate (ORR) of DSP-7888 Dosing Emulsion Administered With Pembrolizumab in Patients With Platinum-resistant Ovarian Cancer (PROC).

  Defined as the proportion of patients who have achieved confirmed Complete Response or Partial Response by RECIST v1.1 based on investigator assessment.

  Radiographic imaging every 6 weeks for 24 weeks and then every 12 weeks until progression for an average of 12 months

Secondary Outcomes (16)

• Phase Ib: The Objective Response Rate (ORR) of DSP-7888 Dosing Emulsion Administered With Pembrolizumab or Nivolumab

  At 4 weeks for the nivolumab arm and at 6 weeks for the pembrolizumab arm and then at Weeks 12, 18, and 24 after the first dose of the DSP-7888 dosing emulsion

• Phase Ib: The Disease Control Rate (DCR) of DSP-7888 Dosing Emulsion Administered With Pembrolizumab or Nivolumab

  At 4 weeks for the nivolumab arm and at 6 weeks for the pembrolizumab arm and then at Weeks 12, 18, and 24 after the first dose of the DSP-7888 dosing emulsion

• Phase Ib: Assessment of the Duration of Response (DOR) of Ombipepimut-S in Combination With Nivolumab or Pembrolizumab

  At week 4 for patients on the nivolumab arm and week 6 for patients on the pembrolizumab arm. Thereafter weeks 12, 18 and 24 and every 12 weeks until progression or death.

• Phase Ib: Progression-free Survival (PFS) of DSP-7888 Dosing Emulsion Administered With Pembrolizumab or Nivolumab

  Radiographic imaging every 6 weeks for 24 weeks and then every 12 weeks until progression for an average of 12 months

• Phase Ib: The 6-month Progression-free Survival (PFS) Rate of Ombipepimut-S in Combination With Nivolumab or Pembrolizumab

  6 months

Study Arms (2)

DSP-7888 Dosing Emulsion in combination with Nivolumab

EXPERIMENTAL

Drug: DSP-7888 Dosing Emulsion; Drug: Nivolumab

DSP-7888 Dosing Emulsion in combination with Pembrolizumab

EXPERIMENTAL

Drug: DSP-7888 Dosing Emulsion; Drug: Pembrolizumab

Interventions

DSP-7888 Dosing Emulsion DRUG

DSP-7888 Dosing Emulsion will be administered intradermally (ID) every 7 days until cycle 3, and then every 14 days for combination with Nivolumab arm or every 21 days for combination with Pembrolizumab arm.

Also known as: Ombipepimut-S (adegramotide and nelatimotide)

DSP-7888 Dosing Emulsion in combination with Nivolumab; DSP-7888 Dosing Emulsion in combination with Pembrolizumab

Nivolumab DRUG

Nivolumab will be administered in the approved dose and schedule starting on Day 29 of the study.

Also known as: Opdivo

DSP-7888 Dosing Emulsion in combination with Nivolumab

Pembrolizumab DRUG

Pembrolizumab will be administered in the approved dose and schedule starting on Day 22 of the study.

Also known as: Keytruda

DSP-7888 Dosing Emulsion in combination with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Patients must fulfill each of the following requirements:
• Phase 1b Dose Search Part Only: A histologically or cytologically confirmed cancer that is metastatic and is approved to be treated with nivolumab or pembrolizumab with the following origins:
• Nivolumab: unresectable or metastatic melanoma, metastatic NSCLC, advanced RCC, recurrent or metastatic squamous cell carcinoma of the head and neck, locally advanced or metastatic urothelial carcinoma, hepatocellular carcinoma, MSI-H/dMMR colorectal cancer
• Pembrolizumab: unresectable or metastatic melanoma, metastatic NSCLC, recurrent or metastatic squamous cell carcinoma of the head and neck, locally advanced or metastatic urothelial carcinoma, unresectable or metastatic MSI-H/dMMR solid tumors, recurrent locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma, recurrent or metastatic cervical cancer
• In addition, the following requirements must be fulfilled:
• Patients must not be considered eligible for a potentially curative resection.
• Patients who are eligible for PD-1 therapy based on either criterion (i) or (ii) below:
• (i) Patients progressed on their prior treatment before initiating treatment on current study, OR (ii) Patients who are currently being treated with nivolumab or pembrolizumab and have achieved at least stable disease (SD), and who, in the judgment of their treating physicians, could benefit from the addition of DSP-7888 Dosing Emulsion vaccine to improve or maintain their response.
• Phase 1b Enrichment Cohort Only: Patients with locally advanced or metastatic RCC or urothelial carcinoma who have experienced disease progression per iRECIST (iCPD) during or within 3 months of last dose of the most recent prior anti-PD-1/ PD-L1-based treatment
• Patients must be positive for at least 1 of the following human leukocyte antigens:
• HLA-A\*02:01
• HLA-A\*02:06
• HLA-A\*24:02
• HLA-A\*03:01
• HLA-B\*15:01

You may not qualify if:

• Patients with any of the following will be excluded from the study:
• Anticancer chemotherapy (including molecular targeted drugs), immunotherapy, radiotherapy, or investigational agents within 4 weeks of the first dose of DSP 7888 Dosing Emulsion
• Major surgery within 4 weeks prior to study treatment
• Patients who have received a live vaccine within 4 weeks prior to the first dose
• Any known, untreated brain metastases; patients with treated brain metastases must be clinically stable for 4 weeks after completion of treatment for brain metastases and have radiographic image documentation of stability. Patients must have no clinical symptoms from brain metastases and not have required systemic corticosteroids \> 10 mg/day prednisone or equivalent for at least 2 weeks prior to the first dose of study drug
• Patients who have multifocal glioblastoma
• Pregnant or breastfeeding
• Patients who have an active autoimmune disease requiring immunosuppression \> 10 mg/day prednisone or equivalent a. Patients with controlled hyperthyroidism must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to study drug administration
• Patients who have interstitial lung disease or active, non-infectious pneumonitis
• Known hypersensitivity to a component of protocol therapy:
• Patients with known hypersensitivity to any of the components of DSP-7888 Dosing Emulsion.
• Patients with known hypersensitivity to nivolumab or pembrolizumab are excluded from receiving combination therapy that includes the agent to which they are hypersensitive
• Uncontrolled concurrent illness including, but not limited to: ongoing or active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy; clinically significant non-healing or healing wounds; symptomatic congestive heart failure; unstable angina pectoris; severe and/or uncontrolled cardiac arrhythmia; significant pulmonary disease; or, psychiatric illness/social situations that would limit compliance with study requirements
• Patients with a history of another primary cancer with the exception of: (a) curatively resected non-melanoma skin cancer; (b) curatively treated cervical carcinoma in situ; (c) localized prostate cancer not requiring systemic therapy; and d) any another cancer from which the patient has been disease free for ≥ 2 years that, in the opinion of the Investigator and medical monitor for the Sponsor, will not affect patient outcome in the setting of the current diagnosis
• Patients who have a QTcF (QT corrected based on Fridericia's equation) interval \> 480 msec (CTCAE = Grade 2) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalemia, family history of long QT interval syndrome) at screening

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (19)

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

St Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

UC Health, LLC

Cincinnati, Ohio, 45229, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

West Cancer Clinic

Germantown, Tennessee, 38138, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Summit Cancer Centers

Spokane, Washington, 99208, United States

Location

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

SMBD Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Fallopian Tube Neoplasms; Wilms Tumor; Ovarian Neoplasms; Kidney Neoplasms; Urinary Bladder Neoplasms

Interventions

Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genital Neoplasms, Female; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Diseases; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Mimi M. Lee, MSW, CCRP
• Organization: Sumitomo Pharma America

mimi.lee@oncology.sumitomo-pharma.com

617-674-6800

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: October 9, 2017
• First Posted: October 17, 2017
• Study Start: December 14, 2017
• Primary Completion: October 19, 2022
• Study Completion: November 29, 2022
• Last Updated: April 18, 2024
• Results First Posted: April 18, 2024

Record last verified: 2024-03

Locations

US (17); CA (2)