ENB003 Plus Pembrolizumab Phase 1b/2a in Solid Tumors

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Cancer, Melanoma, Ovary Cancer, Pancreatic Cancer, Solid Tumor

In brief

First-in Human study evaluating the safety, tolerability and efficacy of ENB003 in combination with Pembrolizumab in solid tumors. The study is separated into two parts. Part A is a 3+3 dose escalation to define the recommended RP2D; this part will include metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer patients subjects, but other solid tumors will be allowed. Once the RP2D is selected, the study will be expanded into metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer subjects. A small number of sarcoma subjects will be included, as exploratory.

Key facts

Study ID

NCT04205227

Run by

ENB Therapeutics, Inc

People needed

137

Starts

2020-02-18

Expected to finish

2026-03-31

Last updated by the study team

2024-09-19

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Malignant Melanoma
• Histopathologically confirmed diagnosis of advanced, unresectable or metastatic malignant melanoma.
• Subjects may have received no more than 3 previous lines of systemic anti-cancer therapy for advanced disease.
• Subjects must have progressed on treatment with an anti-PD1/Ligand 1 (L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression as defined by meeting all of the following criteria:
• Has at least six weeks of anti PD-1/L1 exposure with an approved anti-PD-1/L1 mAb.
• Has a best objective response (according to RECIST) of PD or SD < 6 months. If RECIST not performed, must be determined to have clinical progression within 6 months of initial treatment with anti-PD1 / PD-L1.
• Ovarian Cancer
• Histologically proven diagnosis of high grade serous, high grade endometroid or clear cell ovarian cancer, fallopian tube or primary peritoneal carcinoma.
• Platinum refractory disease, defined as PD during the administration period of first-line platinum-based chemotherapy. Platinum resistant disease defined as PD within 6 months (182 days) after last receipt of first-line platinum-based chemotherapy.
• Subjects may have received up to 3 previous lines of systemic anti-cancer therapy for advanced disease.
• Ovarian cancer patients must be tested for the MSI phenotype. If subjects have high microsatellite instability (MSI-H) or mismatch-repair deficiency (dMMR) phenotype they must have been previously treated with anti-PD1 and demonstrated either PD or disease stabilization, for less than 6 months as best response.
• Pancreatic Cancer
• Histologically confirmed (previously obtained biopsied) metastatic or locally advanced unresectable pancreatic adenocarcinoma or pancreatic adenocarcinoma that is recurrent after resection, including with intraductal papillary mucinous neoplasm.
• Subjects must have previously received and progressed on FOLFIRINOX or a gemcitabine-based regimen for their pancreatic cancer.
• Subjects may have received no more than 2 previous lines of therapy for advanced/metastatic disease.
• Pancreatic cancer patients must be tested for the MSI phenotype. If subjects have high microsatellite instability (MSI-H) or mismatch-repair deficiency (dMMR) phenotype they must have been previously treated with anti-PD1 and demonstrated either PD or disease stabilization for less than 6 months as best response.
• Basket Study:
• The first 10 subjects for each indication must be ETBR+.
• Subjects must have progressed on at least one standard of care therapy and must not have received more than 3 prior systemic therapies.
• SCC of the Head and Neck
• Histologically confirmed metastatic SCC of the head and neck.
• Subjects must have progressed on treatment with an anti-PD1/Ligand 1 (L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression as defined by meeting all of the following criteria:
• Has at least six weeks of anti PD-1/L1 exposure with an approved anti-PD-1/L1 mAb.
• Has a best objective response (according to RECIST) of PD or SD < 6 months
• If RECIST not performed, must be determined to have clinical progression within 6 months of initial treatment with anti-PD1 / PD-L1.

You may not qualify if…

• Subjects will be excluded if they fulfill any of the following exclusion criteria:
• Pregnancy Exclusion
• A WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required.
• Is breastfeeding or expecting to conceive or father children within the projected duration of the study, from the day date of informed consent through to 150 days after the last dose of study treatment for females, and 120 days after the last dose of study treatment for males.
• Prior/Concomitant Therapy
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whichever is shorter, prior to treatment.
• Note: Subjects must have recovered from all AEs due to previous therapies to ≤Grade 1 severity or baseline. Subjects with ≤Grade 2 neuropathy may be eligible at Investigator's discretion. Subjects with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the surgery prior to starting study treatment, as determined by the Investigator.
• Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Note: Subjects must have recovered from all radiation-related toxicities, and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Prior/Concurrent Clinical Study Experience
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Subjects who have entered the follow-up phase of an investigational study may participate provided it has been 4 weeks after the last dose of the previous investigational agent.
• Diagnostic Assessments
• Average Fridericia-corrected QT interval (QTcF) >460 msec for males and QTcF >480 msec for females as measured by electrocardiogram (ECG) at Screening.
• A family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Subjects with basal cell carcinoma of the skin, SCC of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Has severe hypersensitivity (≥ Grade 3) to ENB-003 and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

Where it is running

• Cedars Sinai-The Angeles Clinic — Los Angeles, California, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Border Medical Oncology — Albury, New South Wales, Australia
• Blacktown Oncology — Blacktown, New South Wales, Australia
• Kinghorn-St Vincent's Hospital — Darlinghurst, New South Wales, Australia

Full record on ClinicalTrials.gov

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