Cancer, Colorectal Cancer, Gynecologic Cancer, Head and Neck Cancer, Kidney Cancer, Non Small Cell Lung Cancer, Pancreas Cancer, Skin Cancer, Solid Tumor
Conditions
Keywords
Cytokine, IL-2, Interleukin 2, IL-10, Interleukin 10, Oncology, Immuno-oncology, DK210(EGFR), Immunotherapy, DEKA, DEKA Biosciences
Brief summary
This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.
Detailed description
This study will evaluate DK210(EGFR) as monotherapy and combination in subjects with advanced solid EGFR expressing cancers with documented progressive disease after at least one line of systemic treatment (staging performed by local standard).
Interventions
BIOLOGICALDK210 (EGFR)
Solution for SC administration
RADIATIONRadiation therapy
Short regimen radiation therapy (10 fractions or less)
BIOLOGICALImmune checkpoint blockers
IV administration of approved PD1 blocker
DRUGChemotherapy
Single agent or combination of not more than two
Sponsors
DEKA Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ECOG performance status of 0-1 * Life expectancy of \>3 months according to the investigator's judgment * Solid tumors known for response on Il-2 or Il-10 and/or high expression of EGFR like all Non-small cell Lung, Skin, Head and Neck, Colon, Kidney, Bladder, Pancreatic cancers and all squamous cell carcinoma of other organs can be included with a classical histology report, specific EGFR expression or amplification reports are needed for other solid tumor types like gynecologic, prostate or triple negative breast cancer * Measurable disease, defined as at least one (non-irradiated) lesion measurable on CT/MRI or bone scan as defined by RECIST 1.1. * Progressive disease (PD) at study entry defined as one or more of the following criteria: * Clinical PD with performance decline, clinical symptoms and/or observed tumor growth * PD documented with imaging showing at least 20% growth (largest diameter) and/or new lesions * Adequate cardiovascular, hematological, liver, and renal function. * Subjects have failed one or more lines of systemic therapy and have not been operated on or receiving anti-cancer medication for at least 4 weeks. * Males and females of childbearing potential must agree to use effective contraception starting prior to the first day of treatment and continuing during treatment * Additional criteria may apply
Exclusion criteria
* Subjects with documented diffuse peritoneal disease or persistent abundant ascites * Subjects with known prolonged QtC interval * Concomitant or recent (\<4 weeks or 5 half-lives of the last treatment, whichever is shorter) treatment with agents with anti-tumor activity, including immunotherapies, or experimental therapies. Bone treatments and supportive care can be continued * Major surgery within 4 weeks, Radiation therapy for the treatment of metastases within less than 3 weeks (if single fraction of radiotherapy, then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening * Uncontrolled intercurrent illness including, but not limited to, ongoing and uncontrolled infection (TBC, COVID or HIV patients treated with at least two anti-retroviral drugs and control of their infection with at least 500 /mm3 CD4+ T-cells in their blood and patients cured from Hepatitis B or C (i.e negativity of PCR) and liver function compatible with eligibility criteria are allowed to participate), multiple myeloma, multiple sclerosis, myasthenia gravis, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement * Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) with DK210 (EGFR) | Minimum of 90 days from initiation of experimental therapy | Based on toxicities observed |
| Identify recommended dose of DK210 (EGFR) | Initiation of therapy up to day 90 | Based on toxicities observed |
| Incidence of Adverse Events (AE) of DK210 (EGFR) in combination with radiation, chemotherapy, or checkpoint blockers in Parts B, C, D | Minimum of 90 days from initiation of experimental therapy | Based on toxicities observed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Assessed up to 24 months | Time from first dose of DK210 (EGFR) to the time of death |
| Serum concentrations of DK210 (EGFR) will be determined at various time points | From initiation of treatment through 12 months (every 9 weeks) | Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level |
| Overall response rate (ORR) | Initiation of therapy up to approximately 12 months | Overall response rate (ORR) will be based on clinical examination and investigator review of radiographic images |
| Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points | From initiation of treatment through day 63 | Results will be summarized by dose level |
| Serum concentrations of proinflammatory cytokines such as IL-6, IL-10, TNFa, IL-1b, and interferon (IFN)-g will be assessed at various time points | From initiation of treatment through 12 months (every 9 weeks) | Results will be summarized by dose level |
| Serum will be assayed for the presence of anti-DK210 (EGFR) antibodies | From initiation of treatment through 12 months (every 9 weeks) | Results will be summarized by dose level |
| Best response rate at 9 weeks | Initiation of therapy through Day 63 | Based on investigator clinical examination and review of radiographic images |
| Progression-free (PFS) | Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months | Time from first dose of DK210 (EGFR) to first documentation of clinical or radiographic disease progression or death due to any cause, whichever occurs first. |
Countries
United States
Outcome results
None listed