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

Sponsor

DEKA Biosciences (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05704985

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Solid Tumor Colorectal Cancer Pancreas Cancer Non Small Cell Lung Cancer Head and Neck Cancer Gynecologic Cancer Skin Cancer Kidney Cancer	Biological: DK210 (EGFR) Radiation: Radiation therapy Biological: Immune checkpoint blockers Drug: Chemotherapy	Phase 1

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DK210 (EGFR) Monotherapy (Dose escalation and expansion) 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) Solution for SC administration
Experimental: DK210 (EGFR) + chemotherapy 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) Solution for SC administration Drug: Chemotherapy Single agent or combination of not more than two Other Names: Paclitaxel Carboplatin Oxaliplatin Fluorouracil Capecitabine
Experimental: DK210 (EGFR) + radiation 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) Solution for SC administration Radiation: Radiation therapy Short regimen radiation therapy (10 fractions or less)
Experimental: DK210 (EGFR) + immunotherapy 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) Solution for SC administration Biological: Immune checkpoint blockers IV administration of approved PD1 blocker Other Names: Pembrolizumab Nivolumab

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
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.
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ECOG performance status of 0-1
Life expectancy of >3 months according to the investigator's judgment
By local standard confirmed progressive metastatic and/or locally advanced unresectable solid cancer with EGFR overexpression or amplification
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