CMP-001 and INCAGN01949 for Patients With Stage IV Pancreatic Cancer and Other Cancers Except Melanoma

NCT04387071 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: 0C-19-19/TGen 19-001NCI-2020-03144P30CA014089
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

This phase Ib/II trial studies the side effects and best dose of CMP-001 and how well it works when given together with INCAGN01949 in treating patients with stage IV pancreatic cancer and other cancers except melanoma. CMP-001 is made up of a short piece of DNA that is packaged in a protein, known as a virus-like particle (VLP). VLPs are detected and processed by cells of the immune system. The DNA contained in CMP-001 activates the immune system and recruit cells of the immune system to the tumor. INCAGN01949 is an antibody, a type of protein, which has been shown to stimulate the immune system. Injecting CMP-001 and INCAGN01949 directly into the tumor may work against tumor cells to slow tumor growth by causing tumor cells to die.

Conditions

Locally Advanced Malignant Solid Neoplasm; Metastatic Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate

  Defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the sum of the diameters of the target lesions compared to the baseline; Stable Disease = Neither enough shrinkage for PR nor enough growth for PD; Progressive Disease = at least a 20% increase in the sum of the diameters of the target lesions from the smallest measurement recorded, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. All proportions will be estimated using an exact 95% binomial confidence interval.

  Through end of treatment, up to 2 months

• Objective Response Rate (CR + PR)

  Will be evaluated using the RECIST 1.1 and iRECIST. Changes (i.e. improvements) in tumor measurements from baseline values will be assigned a status of complete response (CR) or partial response (PR) or stable disease (SD). Objective response measurements will comprise the sum of CR plus PR.

  Through end of treatment, up to 2 months.

Secondary Outcomes (3)

• Incidence of Adverse Events

  Through study completion, up to 9 months

• Progression Free Survival (PFS)

  Through study completion, up to 9 months

• Overall Survival

  Through study completion, up to 9 months

Other Outcomes (5)

• OX40 Expression Within the Lymphocyte Subsets (Effector T Cell [Teff] and Regulatory T Cell [Treg])

  Through study completion, up to 9 months

• Enumeration of CD4+ and CD8+ T Cell Subsets

  Through study completion, up to 9 months

• Expression of Activation/Differentiation Markers on CD4+ and CD8+ T Cell Subsets

  Through study completion, up to 9 months

Study Arms (7)

Dose Level 1 (CMP-001, INCAGN01949)

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 500 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level -1 (CMP-001, INCAGN01949)

EXPERIMENTAL

Arm Description: Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 250 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level 2 (CMP-001, INCAGN01949)

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 1000 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level 3 (CMP-001, INCAGN01949)

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 1670 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level 4 (CMP-001, INCAGN01949

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 2505 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level 5 (CMP-001, INCAGN01949)

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 3507 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Dose Level 6 (CMP-001, INCAGN01949)

EXPERIMENTAL

Patients receive CMP-001 at 5 mg SC on day 1 of weeks 1 and 2 and 10 mg IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity. Patients also receive INCAGN01949 at 4559 mcg/m\^2 IT on day 1 of weeks 3-6 in the absence of disease progression or unacceptable toxicity.

Biological: Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949; Drug: VLP-encapsulated TLR9 Agonist CMP-001

Interventions

VLP-encapsulated TLR9 Agonist CMP-001 DRUG

Given SC and IT

Also known as: ARB-1598, CMP-001, CYT 003, CYT-003

Dose Level -1 (CMP-001, INCAGN01949); Dose Level 1 (CMP-001, INCAGN01949); Dose Level 2 (CMP-001, INCAGN01949); Dose Level 3 (CMP-001, INCAGN01949); Dose Level 4 (CMP-001, INCAGN01949; Dose Level 5 (CMP-001, INCAGN01949); Dose Level 6 (CMP-001, INCAGN01949)

Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949 BIOLOGICAL

Given IT

Also known as: Anti-OX40 Agonist Antibody INCAGN01949, Anti-OX40 Monoclonal Antibody INCAGN0194, INCAGN 1949, INCAGN-1949, INCAGN1949, Monoclonal Antibody INCAGN01949, NCAGN01949

Dose Level -1 (CMP-001, INCAGN01949); Dose Level 1 (CMP-001, INCAGN01949); Dose Level 2 (CMP-001, INCAGN01949); Dose Level 3 (CMP-001, INCAGN01949); Dose Level 4 (CMP-001, INCAGN01949; Dose Level 5 (CMP-001, INCAGN01949); Dose Level 6 (CMP-001, INCAGN01949)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis or other locally advanced un-resectable solid tumor malignancies (during the phase Ib and pancreatic cancer during phase II) deemed appropriate by the investigator except melanoma
• Patients will have had at least 2 prior therapies for locally advanced, unresectable and/or metastatic disease. Adjuvant therapy will count as one line of therapy if disease progression occurred during treatment or within 6 months of completion. Patients with metastatic pancreatic cancer must have received either fluorouracil/Irinotecan/leucovorin calcium/oxaliplatin (FOLFIRINOX) or a gemcitabine-based regimen as one of their prior lines of therapy. Patients with germline BRCA mutations must have received olaparib as maintenance therapy
• Be willing to undergo an image-guided biopsy of a tumor lesion at baseline, after 2 weeks of IT injection and 4 weeks of IT injection (week 4 and 6), unless tumor is considered inaccessible or biopsy is otherwise considered not in the patients best interest
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Subjects must have at least one extra-central nervous system (CNS), non-bone tumor lesion amenable for IT injection \>= 1.5 cm and that is not in close proximity or encasing crucial structures such as major blood vessels, trachea, nerve bundles etc. Measurable disease is required in a minimum of two lesions (one injected and one other) and there must be at least one measurable lesion in addition to the one being injected
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL without transfusions within 7 days of assessment (transfusions are allowed prior to this period)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 X ULN OR
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine transferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Investigator. If patients received prior ipilimumab or anti-CTLA4 compound and had adrenal insufficiency, treat these subjects with stress dose steroids prior to intratumoral injections. Patients may receive stress steroids orally or intravenously (IV) before the procedure
• Hypersensitivity to CMP-001 (TLR9 agonist) or INCAGN01949 (anti-OX40) or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to week 1/day 1, or who has not recovered (i.e., =\< grade 1 or to baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, investigational agent, targeted small molecule therapy, or radiation therapy within 3 weeks (or 5 half-lives whichever is shorter) prior to week 1/ day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent(s)
• Note: Patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the trial
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Other malignancies which have been treated with curative intent, or for which patients are not receiving active therapy, may be considered upon discussion with the investigator
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. Use of prophylactic anti-epileptic drugs is permitted. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active bacterial infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has active hepatitis B or C. Treated hepatitis C with sustained virologic response, and patients who are negative for hepatitis B surface antigen (sAg) are not excluded

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

CYT003-QbG10

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Tali Homsey
• Organization: USC/Norris Comprehensive Cancer Center

Tali.Homsey@med.usc.edu

(323) 865-0451

Study Officials

• Diana L Hanna, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 9, 2020
• First Posted: May 13, 2020
• Study Start: April 29, 2021
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: April 17, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-02

Locations

US (4)