Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

NCT02387125 | Terminated Phase 1 DMC

• 2 other identifiers: V943A-001IMDZ-C131
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered LV305 \[a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene\] and G305 \[NY-ESO-1 recombinant protein plus GLA-SE\]) in patients with melanoma, sarcoma, ovarian cancer, or non-small cell lung cancer that express NY-ESO-1.

Conditions

Sarcoma; Melanoma; Non-small Cell Lung Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• The nature, frequency and severity of adverse events (AEs) and laboratory abnormalities in subjects receiving CMB305 alone or in combination with oral metronomic CPA or G100

  To evaluate the safety and tolerability of CMB305 (sequential administered doses of LV305 and G305) alone or in combination with oral metronomic CPA or G100 in subjects with locally advanced, relapsed, or metastatic cancer expressing NY ESO 1

  Up to 5 years since first study injection

Secondary Outcomes (4)

• Time to Progression

  Up to 5 years since first study injection

• Progression Free Survival

  Up to 5 years since first study injection

• Overall Survival

  Up to 5 years since first study injection

• Humoral and cellular immune responses at selected sites, as measured by changes from baseline anti-NY-ESO-1 immunity

  Approximately 14 weeks

Other Outcomes (2)

• To evaluate pre- and post-regimen blood samples for potential biomarkers of immunogenicity and clinical tumor response

  Approximately 14 weeks

• To evaluate available pre- and post-regimen tumor tissue for histologic, immunohistologic, and genomic markers following administration of CMB305 alone or in combination with mCPA or G100

  Approximately 14 weeks

Study Arms (2)

Part 1 Dose Escalation of CMB305

EXPERIMENTAL

Patients with melanoma, NSCLC, ovarian cancer, or sarcoma will be enrolled. Patients will receive CMB305, a sequential regimen of LV305 and G305. Two cohorts are planned based on LV305 dose.

Biological: CMB305

Part 2 Expansion of CMB305

EXPERIMENTAL

Arm A will enroll up to 9 patients each with NSCLC or ovarian cancer, or up to 18 patients with the sarcoma subtypes, synovial sarcoma or MRCL. Arm B will enroll up to 9 additional patients with selected sarcoma subtypes to explore subcutaneous (SC) dosing of LV305 and G305 on the same schedule. Arm C will enroll up to 9 patients with synovial sarcoma or MRCL for treatment with CMB305 and with oral metronomic CPA. Arm D will enroll up to 9 patients with synovial sarcoma or MRCL at selected sites for treatment with CMB305 and IT G100. Arm E will enroll up to 6 patients with soft tissue sarcoma any subtype for treatment with a higher dose of CMB305 than previous arms.

Biological: CMB305; Biological: G100; Drug: Metronomic CPA

Interventions

CMB305 BIOLOGICAL

Part 1 Dose Escalation of CMB305; Part 2 Expansion of CMB305

G100 BIOLOGICAL

Part 2 Expansion of CMB305

Metronomic CPA DRUG

Also known as: Cytoxan Tablets

Part 2 Expansion of CMB305

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced, relapsed, and/or metastatic cancer
• Tumor histology consistent with one of the following: In Part 1, Dose Escalation - melanoma, NSCLC, ovarian cancer (including fallopian tube carcinoma), or sarcoma (any subtype). In Part 2, Patient Expansion - NSCLC, ovarian cancer (including fallopian tube carcinoma), or the sarcoma subtypes, synovial sarcoma or myxoid/round cell liposarcoma
• Tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR. At least one tumor must be accessible and patients must consent for biopsies in Arms C and D.
• Inadequate response, relapse, and/or unacceptable toxicity with one or more prior systemic, surgical, or radiation cancer therapies, and for whom curative standard therapy is not an option (except patients with NSCLC who must have experienced either an inadequate response, relapse, and/or unacceptable toxicity with two or more prior systemic, surgical, or radiation cancer therapies)
• \. ≥ 18 years of age 7. Life expectancy of ≥ 6 months per the investigator 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 9. ECG without evidence of clinically significant arrhythmia or ischemia 10. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use at least one highly effective or two effective contraceptive methods during the dosing period and for three months after last CMB305 injection 11. If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom during the dosing period and for three months after last CMB305 injection

You may not qualify if:

• Investigational therapy within 3 weeks prior to CMB305 dosing
• Prior administration of other NY-ESO-1-targeting immunotherapeutics
• Significant immunosuppression from:
• Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or
• Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine (antihistamines, non-steroidal anti-inflammatory drugs and aspirin permitted) or conditions such as common variable hypogamma-globulinemia or exposures such as large field radiotherapy
• Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors, G-CSF or GM-CSF within 3 weeks prior to the first scheduled CMB305 dosing
• Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent
• Significant autoimmune disease with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy
• Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
• Inadequate organ function including:
• Marrow: Peripheral blood leukocyte count (WBC) \< 3000/mm3, absolute neutrophil count ≤ 1500/mm3, platelets \< 75000/mm3, or hemoglobin \< 10 gm/dL
• Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) \> 2.5 x ULN, total serum bilirubin \> 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL)
• Renal: Creatinine \> 1.5x ULN
• Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) \>1.5 x ULN
• History of other cancer within 3 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ).

Sponsors & Collaborators

• Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (8)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267-0502, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98102, United States

Location

MeSH Terms

Conditions

Sarcoma; Melanoma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms

Interventions

TLR4 agonist G100; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; 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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

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: March 1, 2015
• First Posted: March 12, 2015
• Study Start: February 28, 2015
• Primary Completion: March 29, 2019
• Study Completion: March 29, 2019
• Last Updated: July 1, 2020

Record last verified: 2020-06

Locations

US (8)