Safety, Tolerability, and Anti-Tumor Activity of AFM24 in Combination With SNK01 in Subjects With Advanced/Metastatic EGFR-Expressing Cancers

A Phase 1/2a, Open-Label, Multi-Center Study Evaluating the Safety, Tolerability, and Anti-Tumor Activity of AFM24 in Combination With Ex Vivo Expanded Autologous Natural Killer Cells (SNK01) in Subjects With Advanced/Metastatic EGFR-Expressing Cancers

This is an open-label, multi-center study to evaluate the safety, tolerability, and anti-tumor activity of SNK01 in combination with AFM24 in subjects with advanced or metastatic EGFR-expressing cancers.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Advanced Solid Tumor; Metastatic Tumor; Refractory Tumor
• Intervention / Treatment: Drug: AFM24; Biological: SNK01

Detailed Description

The study will be conducted in two phases. The Phase 1/dose escalation phase will gather preliminary safety and tolerability data for escalating doses of AFM24 in combination with SNK01 at a fixed dose in order to determine the MTD/RP2D for the combination dose regimen to be used in the Phase 2a/expansion.

The Phase 2a/expansion portion of the study will gather additional safety, tolerability, efficacy, and anti-tumor activity information for the combination of AFM24 with SNK01 in subjects with three types of advanced or metastatic EGFR-expressing cancers.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: NKGen Biotech, Inc.; Phone Number: 9493966830; Email: trials@nkgenbiotech.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Capable of giving signed informed consent
2. Males and females age ≥ 18 years
3. Phase 1/Dose Escalation : any histologically confirmed advanced or metastatic EGFR-positive malignancy for which all standard of care treatment options have been received and are no longer effective or are considered inappropriate at the discretion of the investigator.
4. Phase 2a/Expansion : histologically confirmed advanced or metastatic EGFR positive malignancy of mCRC (EXP-1 cohort), SCCHN (EXP-2 cohort) or NSCLC (EXP-3 cohort).

5. Additional Criteria for Phase 2a/Expansion: subjects must have a disease history specific to their disease as listed below:

   1. EXP-1: mCRC. Metastatic colorectal cancer (mCRC) MSI low/DNA mismatch repair proficient. Subjects must have received ≥ 1 lines of previous combination therapy and must have been exposed to oxaliplatin, irinotecan, a fluoropyrimidine, a VEGF targeting agent and, if considered appropriate by the treating physician, an EGFR targeted antibody.
   2. EXP-2: SCCHN. Subjects with advanced or metastatic SCCHN whose disease has progressed after having received ≥ 1 prior lines of therapy for advanced disease, which must have included platinum-based therapy, fluoropyrimidine, and an anti PD 1/PD-L1 antibody.
   3. EXP-3: NSCLC. Subjects with advanced or metastatic EGFR-expressing NSCLC (EGFR WT) whose disease has progressed after having received ≥ 1 prior lines of therapy for advanced disease. Subjects must have received at least a platinum-based doublet in combination with anti-PD1/PD-L1 antibody or must have received a platinum-based doublet followed by an anti-PD1/PD-L1 antibody.
6. One or more measurable tumors lesions per RECIST v1.1
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Adequate bone marrow, hepatic and renal function.

Key Exclusion Criteria:

1. Superior vena cava syndrome contra-indicating hydration
2. Untreated or symptomatic central nervous system (CNS) metastases
3. No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤ 1 according to the NCI-CTCAE v.5.0 (except peripheral or motor neuropathy, lymphopenia and alopecia)
4. Treatment with systemic anticancer therapy or an investigational device within 4 weeks (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of the agent (if half-life is known and it is shorter) before the first dose of study treatment.
5. Radiation therapy within 2 weeks before first dose of any study treatment or unresolved (NCI CTCAE v5.0 Grade > 1) toxicity from previous radiotherapy
6. Clinically significant cardiovascular disease
7. Major surgery within 4 weeks prior to any study treatment administration
8. Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol
9. Active uncontrolled viral, fungal, or bacterial infection requiring systematic therapy within 14 days prior to first dose of study treatment.
10. Known history of testing positive for human immunodeficiency virus (HIV), and/or positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
11. Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring systemic immunosuppressive therapy
12. A serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
13. Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1, Dose Escalation; It is estimated that approximately 3-6 subjects will be enrolled per cohort in three dose cohorts for a total of 12-18 participants. SNK01 (fixed dose) will be administered weekly by IV infusion.	Drug: AFM24; Tetravalent, bispecific EGFR- and CD16A-binding innate cell engager.; Biological: SNK01; Patient-specific ex-vivo expanded autologous natural killer cells.
Experimental: Phase 2a, Expansion Cohort 1 - Metastatic colorectal cancer (EXP-1: mCRC); SNK01 (fixed dose) will be administered weekly by IV infusion.	Drug: AFM24; Tetravalent, bispecific EGFR- and CD16A-binding innate cell engager.; Biological: SNK01; Patient-specific ex-vivo expanded autologous natural killer cells.
Experimental: Phase 2a, Expansion Cohort 2 - Head and Neck Squamous Cell Carcinoma (EXP-2: SCCHN); SNK01 (fixed dose) will be administered weekly by IV infusion.	Drug: AFM24; Tetravalent, bispecific EGFR- and CD16A-binding innate cell engager.; Biological: SNK01; Patient-specific ex-vivo expanded autologous natural killer cells.
Experimental: Phase 2a, Expansion Cohort 3 - Non-small cell lung cancer (EXP-3: NSCLC); SNK01 (fixed dose) will be administered weekly by IV infusion.	Drug: AFM24; Tetravalent, bispecific EGFR- and CD16A-binding innate cell engager.; Biological: SNK01; Patient-specific ex-vivo expanded autologous natural killer cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/Dose Escalation	Determine the maximum tolerated dose (MTD) of AFM24 in combination with SNK01. To be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period.	28 days starting on cycle 1 day 1
Phase 1/Dose Escalation	Determine the recommended phase 2 dose (RP2D) of AFM24 in combination with SNK01. To be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period.	28 days starting on cycle 1 day 1
Phase 2a/Expansion	Determine objective response rate (ORR) of AFM24 in combination with SNK01. Determine ORR using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/Dose Escalation	Assess safety and tolerability of AFM24 in combination with SNK01. Determine frequency and severity of treatment-emergent AEs (TEAEs) per National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI CTCAE v 5.0).	Up to 24 months
Phase 1/Dose Escalation	Determine preliminary efficacy of AFM24 in combination with SNK01. Determine ORR using RECIST v1.1 evaluated by local assessment.	Up to 24 months
Phase 1/Dose Escalation	Maximum observed plasma concentration (Cmax) of AFM24	28 days starting on cycle 1 day 1
Phase 1/Dose Escalation	Time to maximum plasma concentration (Tmax) of AFM24	28 days starting on cycle 1 day 1
Phase 1/Dose Escalation	Minimum plasma concentration (Cmin) of AFM24	28 days starting on cycle 1 day 1
Phase 1/Dose Escalation	Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24	28 days starting on cycle 1 day 1
Phase 1/Dose Escalation	Immunogenicity of AFM24 when AFM24 is given in combination with SNK01 Frequency of subjects developing AFM24 anti drug antibodies (ADAs) through completion of the Phase 1/dose escalation portion	Up to 24 months
Phase 2a/Expansion	Safety and tolerability of AFM24 in combination with SNK01 Frequency of TEAEs graded according to NCI CTCAE v 5.0	Up to 24 months
Phase 2a/Expansion	To assess progression-free survival (PFS) according to RECIST v1.1 by local assessment Assess the number of subjects with PFS defined as duration of time from start of combination treatment to date of progression.	Up to 24 months
Phase 2a/Expansion	To assess overall survival (OS).	Up to 24 months
Phase 2a/Expansion	To assess duration of response (DOR) according to RECIST v1.1 by local assessment.	Up to 24 months
Phase 2a/Expansion	To assess clinical benefit rate (CBR) according to RECIST v1.1 by local assessment.	Up to 24 months
Phase 2a/Expansion	Maximum observed plasma concentration (Cmax) of AFM24.	28 days starting on cycle 1 day 1
Phase 2a/Expansion	Time to maximum plasma concentration (Tmax) of AFM24.	28 days starting on cycle 1 day 1
Phase 2a/Expansion	Minimum plasma concentration (Cmin) of AFM24.	28 days starting on cycle 1 day 1
Phase 2a/Expansion	Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24.	28 days starting on cycle 1 day 1
Phase 2a/Expansion	Immunogenicity of AFM24 when AFM24 is given in combination with SNK01 Frequency of subjects developing AFM24 ADAs and frequency of subjects developing neutralizing ADAs.	Up to 24 months

Collaborators and Investigators

• Sponsor: NKGen Biotech, Inc.
• Collaborators: Affimed GmbH
• Investigators: Study Director: Paul Chang, MPH, NKGen Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): September 21, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: October 18, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Refractory; Lung cancer; antibody; EGFR; Metastatic; Natural killer cell; Solid tumor; NK cells; SCCHN; IgG1; EGFR Positive; EGFR+; AFM24; SNK01; CD16A; ADCC; ADCP
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Lung Neoplasms; Carcinoma, Squamous Cell; Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Colorectal Neoplasms; Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: AFM24-SNK01-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No