A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile

NCT03416335 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BBI-DSP0509-101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multi-center, Phase 1 / 2 clinical study for patients with advanced solid tumors. The study consists of 2 treatment arms - a monotherapy arm and a combination arm. The monotherapy arm has 1 part: Dose Escalation (Part A). The combination arm has Dose Escalation (Part B) only.

Conditions

Neoplasms

Keywords

DSP-0509; Toll-Like Receptor 7 (TLR-7); BLRM (Bayesian Logistic Regression Model)

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Dose-limiting Toxicities (DLTs) Within the First 6 Weeks of Dosing

  From the time of first dose to 6 weeks after the first dose

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

  28 days

• Determination of the MTD of DSP-0509 When Given in Combination With Pembrolizumab by Assessing Dose-limiting Toxicities (DLTs).

  MTD of DSP-0509 in patients enrolled into the Combination Arm during the dose escalation part of the study.

  28 days

• Determination of RP2D of DSP-0509 When Given in Combination With Pembrolizumab by Assessing DLTs

  Data to be derived from patients enrolled into the Combination Arm - Part B (Phase 1).

  28 days

• Preliminary Antitumor Activity of DSP-0509 in Combination With Pembrolizumab in Patients With Head & Neck Squamous Cell Carcinoma (HNSCC) Who Have Shown Primary or Acquired Resistance to Immune Checkpoint Inhibitors (ICIs)

  Data to be derived from patients enrolled into the Combination Arm - Part C (Phase 2)

  4 weeks

Secondary Outcomes (10)

• Evaluate Pharmacokinetics (PK) for Single Agent DSP-0509 by Assessing Plasma Concentration.

  8 weeks

• Objective Response Rate (ORR) by RECIST

  From date of first dose to 6 months post first dose

• ORR by Immune RECIST (iRECIST)

  From date of first dose to 6 months post first dose

• Duration of Response (DoR) by RECIST

  6 months

• DoR by iRECIST

  6 months

Other Outcomes (5)

• Identification of Potential Metabolites of DSP-0509 in Plasma and Possibly in Urine.

  8 weeks

• Exploratory Pharmacodynamic Evaluation as Potential Biomarkers Capable of Predicting the Clinical Efficacy or Toxicity

  12 months

• Exploratory Pharmacodynamic Evaluation as Potential Efficacy-related Immune Response Biomarkers.

  12 months

Study Arms (3)

Monotherapy Arm - Part A

EXPERIMENTAL

Dose Escalation Drug DSP-0509

Drug: DSP-0509

Combination arm - Part B

EXPERIMENTAL

Dose Escalation Drug DSP-0509, Pembrolizumab

Drug: DSP-0509, Pembrolizumab

Combination arm - Part C

EXPERIMENTAL

Dose Expansion, Drug DSP-0509, Pembrolizumab

Drug: DSP-0509, Pembrolizumab

Interventions

DSP-0509 DRUG

Each patient treated will receive DSP-0509 at the dose fixed for that Part or cohort administered as a constant rate IV infusion over 10 minutes using a syringe pump.

Monotherapy Arm - Part A

DSP-0509, Pembrolizumab DRUG

Each patient treated will receive DSP-0509 at the dose fixed for that Part or cohort administered as a constant rate IV infusion over 10 minutes using a syringe pump and is given in combination with pembrolizumab which should be administered following the dosing schedule of the approved label (200 mg IV q3w)

Combination arm - Part B

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:
• \. Must have a histologically or cytologically confirmed advanced solid tumor that meets the following additional specifications
• Monotherapy Part A (Dose Escalation) advanced solid tumor that is metastatic or unresectable and recurrent and /or refractory to available therapy.
• Combination Part B (Dose Escalation)- advanced solid tumors that are (a) metastatic or unresectable and recurrent and/or refractory to available therapy; (b) a condition for which pembrolizumab is an approved treatment: and (c) in patients who either have shown primary or acquired resistance to immune checkpoint inhibitors (ICIs)
• Combination Arm C (Dose Expansion), Phase 2 - Advanced HNSCC tumors of the oropharynx, oral cavity, hypopharynx, larynx, lip, or sinus that are (a) metastatic or unresectable, and recurrent and/or refractory to available therapy, (b) in patients who have been treated with pembrolizumab or other PD-1 or PD-L1 inhibitors in monotherapy, and (c) who have subsequently shown primary or acquired resistance to ICIs.
• For enrollment in both arms:
• \. Must be ≥ 18 years of age
• \. Should have all side effects of any prior therapy or procedures for any medical condition recovered to CTCAE ≤ Grade 1 (except alopecia).
• \. Must have at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1.
• \. Must have a life expectancy ≥ 3 to 6 months.
• \. Female patients of childbearing age and women \< 12 months since the onset of menopause, except those who have been surgically sterilized (tubal ligation) or whose sexual partner(s) is surgically sterilized (vasectomy), must agree to use acceptable contraceptive methods for the duration of the study and for 9 months after the date of their last DSP-0509 infusion. If employing contraception, 2 of the following precautions must be used: birth control pill, vaginal diaphragm, intrauterine system or device, condom or vaginal spermicide. Female patients who are postmenopausal are defined as those with an absence of menses for ≥ 12 consecutive months. Male patients must be surgically sterilized (vasectomy) or their female sexual partner(s) must be surgically sterilized (tubal ligation) to avoid using contraception. If they do not meet this criterion, then male patients or must agree to use a condom as well as one of the acceptable contraceptive methods listed above with their female partner(s) who meets the criteria of either being of childbearing age or is \< 12 months since the onset of menopause. Male patients and their female partner(s) must agree to use acceptable contraception methods for the duration of time the male patient is on the study and for 9 months after the date of his last DSP 0509 infusion.
• \. Females of childbearing potential must have a negative serum pregnancy test.
• \. Must have an Eastern Cooperative Oncology Group performance status of 0 to 1.
• \. Must have adequate coagulation function at Screening as determined by:
• a. Prothrombin international normalized ratio \< 1.5. b. Partial thromboplastin time \< 1.5 times the upper limit of normal (ULN).

You may not qualify if:

• Patients with any of the following will be excluded from the study:
• For enrollment in both arms:
• Has received prior therapy with a TLR agonist, excluding a topical TLR agonist.
• Has received anticancer chemotherapy (including molecular-targeted drugs), radiotherapy, immunotherapy (eg, vaccines or cytokines), or investigational agents within the 3 weeks before the first dose of DSP-0509. Local palliative radiotherapy is permitted3. Receives concurrent systemic (oral or IV) steroid therapy \> 10 mg prednisone daily or its equivalent for an underlying condition.
• \. Not fully recovered from major surgery before the first dose of DSP-0509.
• \. Has central nervous system (CNS) metastases (including leptomeningeal metastases, spinal metastases) or CNS primary tumors, eg, glioblastoma.
• \. Has a history of seizures other than isolated febrile seizure in childhood; has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
• \. Has effusions (pleural, pericardial, or ascites) requiring drainage.
• \. Has a neurodegenerative disease, eg, motor neuron disease, Parkinson disease, Alzheimer disease, Huntington disease.
• \. Has retinal detachment, ulcerative keratitis, uveitis, Vogt-Koyanagi-Harada syndrome, choroidal neovascularization, retinopathy/retinitis, thyroid-associated orbitopathy, idiopathic orbital inflammation, diabetic retinopathy, ischemic retinopathy including glaucoma-associated retinopathy, retinal vein thrombosis, or a non-healing ocular or ophthalmic disease.
• \. Has a fever ≥ 38°C within 3 days before the first dose of study treatment.
• \. Has interstitial lung disease or active noninfectious pneumonitis.
• \. Has a history of active autoimmune or immunologic disorder requiring immunosuppression with steroids or other immunosuppressive agents (eg, azathioprine, cyclosporine A) except for patients with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave disease. Patients with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin before study drug administration.
• \. Has a known hypersensitivity to a component of the protocol therapy, DSP-0509, or another pyrimidine.
• \. Has a history of another primary cancer within the 5 years before enrollment except for the following: non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other nonmetastatic carcinoma that has been in complete remission without treatment for more than 5 years.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead
• Syneos Health: collaborator

Study Sites (5)

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 25799, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Henry-Joyce Cancer Center, Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

M.D. Anderson Cancer Center, The University of Texas

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Limitations and Caveats

The sponsor made the decision to terminate the study on August 2022 with all patients removed from treatment and follow-up by December 2022. Consistent with Food and Drug Administration and International Council for Harmonisation guidance on the content for abbreviated and synoptic CSRs, only safety data are analyzed and reported.

Results Point of Contact

• Title: Reyna Bishop
• Organization: Sumitomo Pharma America

reyna.bishop@us.sumitomo-pharma.com

617-674-6800

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: January 31, 2018
• Study Start: June 1, 2018
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: May 30, 2024
• Results First Posted: May 30, 2024

Record last verified: 2024-05

Locations

US (5)