Clinical trial NCT05099549: Safety, Tolerability, and Anti-Tumor Activity of AFM24 in Combination With SNK01 in Subjects With Advanced/Metastatic EGFR-Expressing Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Advanced Solid Tumor
Refractory Tumor
Metastatic Tumor
Keywords: EGFR Positive
EGFR
EGFR+
AFM24
SNK01
Solid tumor
Lung cancer
Refractory
Metastatic
NSCLC
SCCHN
NK cells
Natural killer cell
IgG1
antibody
CD16A
ADCC
ADCP
Lead sponsor: NKGen Biotech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Affimed GmbH
First posted: 2021-10-29
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subjects will be enrolled sequentially in cohorts of 3 to 6 subjects into Phase 1/dose escalation. The dose escalation will follow the standard oncology Phase 1 3 + 3 dose escalation design. A minimum of 3 cohorts will be utilized and dose increases will be determined by the Safety Review Committee.

Once RP2D is determined in Phase 1/dose escalation, the Phase 2a/expansion phase will begin enrolling up to 121 subjects.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
Secondary outcomes:
measure: Phase 1/Dose Escalation
timeFrame: Up to 24 months
measure: Phase 1/Dose Escalation
timeFrame: Up to 24 months
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 1/Dose Escalation
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 1/Dose Escalation
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
measure: Phase 2a/Expansion
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 2a/Expansion
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 2a/Expansion
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 2a/Expansion
timeFrame: 28 days starting on cycle 1 day 1
measure: Phase 2a/Expansion
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: NKGen Biotech, Inc.
name: Paul Chang, MPH
role: STUDY_DIRECTOR
References: