Evaluating Safety and Biomarkers Using DK210 (EGFR) for Locally Advanced or Metastatic EGFR+ Tumors

Study Overview
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Brief Summary
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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
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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).

Official Title
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Dose-finding Phase 1 Trial: Evaluating Safety and Biomarkers Using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors With Progressive Disease Failing Systemic Therapy

Conditions
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Cancer, Solid Tumor, Colorectal Cancer, Pancreas Cancer, Non Small Cell Lung Cancer, Head and Neck Cancer, Gynecologic Cancer, Skin Cancer, Kidney Cancer

Intervention / Treatment
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* Biological: DK210 (EGFR)
* Radiation: Radiation therapy
* Biological: Immune checkpoint blockers
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DK210 (EGFR) Monotherapy (Dose escalation and expansion)<br>DK210 (EGFR) will be administered as monotherapy three times per week via subcutaneous (SC) administration. Dose will be escalated from 0.025 mg/kg to 0.3 mg/kg or until unacceptable toxicity, disease progression, or withdrawal of consent. An expansion cohort at the optimal dose will be enrolled in parallel with the combination arms. | Biological: DK210 (EGFR)<br>* Solution for SC administration<br>|
| Experimental: DK210 (EGFR) + chemotherapy<br>In patients with good tolerance of first line systemic therapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with second-line intravenous (IV) chemotherapy until unacceptable toxicity, disease progression, or withdrawal of consent | Biological: DK210 (EGFR)<br>* Solution for SC administration<br>Drug: Chemotherapy<br>* Single agent or combination of not more than two<br>* Other names: Capecitabine;|
| Experimental: DK210 (EGFR) + radiation<br>In patients with need of palliative radiation, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with short course radiation therapy (10 fractions or less) until unacceptable toxicity, disease progression, or withdrawal of consent | Biological: DK210 (EGFR)<br>* Solution for SC administration<br>Radiation: Radiation therapy<br>* Short regimen radiation therapy (10 fractions or less)<br>|
| Experimental: DK210 (EGFR) + immunotherapy<br>In patients with good tolerance of first line immunotherapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with intravenous (IV) immune checkpoint blockers until unacceptable toxicity, disease progression, or withdrawal of consent | Biological: DK210 (EGFR)<br>* Solution for SC administration<br>Biological: Immune checkpoint blockers<br>* IV administration of approved PD1 blocker<br>* Other names: Nivolumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) with DK210 (EGFR) | Based on toxicities observed | Minimum of 90 days from initiation of experimental therapy | 
| Identify recommended dose of DK210 (EGFR) | Based on toxicities observed | Initiation of therapy up to day 90 | 
| Incidence of Adverse Events (AE) of DK210 (EGFR) in combination with radiation, chemotherapy, or checkpoint blockers in Parts B, C, D | Based on toxicities observed | Minimum of 90 days from initiation of experimental therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Overall response rate (ORR) will be based on clinical examination and investigator review of radiographic images | Initiation of therapy up to approximately 12 months | 
| Best response rate at 9 weeks | Based on investigator clinical examination and review of radiographic images | Initiation of therapy through Day 63 | 
| Progression-free (PFS) | 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. | Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months | 
| Overall Survival (OS) | Time from first dose of DK210 (EGFR) to the time of death | Assessed up to 24 months | 
| Serum concentrations of DK210 (EGFR) will be determined at various time points | Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level | From initiation of treatment through 12 months (every 9 weeks) | 
| Serum will be assayed for the presence of anti-DK210 (EGFR) antibodies | Results will be summarized by dose level | From initiation of treatment through 12 months (every 9 weeks) | 
| Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points | Results will be summarized by dose level | From initiation of treatment through day 63 | 
| 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 | Results will be summarized by dose level | From initiation of treatment through 12 months (every 9 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokine, IL-2, Interleukin 2, IL-10, Interleukin 10, Oncology, Immuno-oncology, DK210(EGFR), Immunotherapy, DEKA, DEKA Biosciences