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

NCT05099549 | Terminated Phase 1 FDA Drug

• 1 other identifier: AFM24-SNK01-103
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (17)

• Phase 1/Dose Escalation

  Up to 24 months

• Phase 1/Dose Escalation

  Up to 24 months

• Phase 1/Dose Escalation

  28 days starting on cycle 1 day 1

• Phase 1/Dose Escalation

  28 days starting on cycle 1 day 1

• Phase 1/Dose Escalation

  28 days starting on cycle 1 day 1

Study Arms (4)

Phase 1, Dose Escalation

EXPERIMENTAL

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; Biological: SNK01

Phase 2a, Expansion Cohort 1 - Metastatic colorectal cancer (EXP-1: mCRC)

EXPERIMENTAL

SNK01 (fixed dose) will be administered weekly by IV infusion.

Drug: AFM24; Biological: SNK01

Phase 2a, Expansion Cohort 2 - Head and Neck Squamous Cell Carcinoma (EXP-2: SCCHN)

EXPERIMENTAL

SNK01 (fixed dose) will be administered weekly by IV infusion.

Drug: AFM24; Biological: SNK01

Phase 2a, Expansion Cohort 3 - Non-small cell lung cancer (EXP-3: NSCLC)

EXPERIMENTAL

SNK01 (fixed dose) will be administered weekly by IV infusion.

Drug: AFM24; Biological: SNK01

Interventions

AFM24 DRUG

Tetravalent, bispecific EGFR- and CD16A-binding innate cell engager.

Phase 1, Dose Escalation; Phase 2a, Expansion Cohort 1 - Metastatic colorectal cancer (EXP-1: mCRC); Phase 2a, Expansion Cohort 2 - Head and Neck Squamous Cell Carcinoma (EXP-2: SCCHN); Phase 2a, Expansion Cohort 3 - Non-small cell lung cancer (EXP-3: NSCLC)

SNK01 BIOLOGICAL

Patient-specific ex-vivo expanded autologous natural killer cells.

Phase 1, Dose Escalation; Phase 2a, Expansion Cohort 1 - Metastatic colorectal cancer (EXP-1: mCRC); Phase 2a, Expansion Cohort 2 - Head and Neck Squamous Cell Carcinoma (EXP-2: SCCHN); Phase 2a, Expansion Cohort 3 - Non-small cell lung cancer (EXP-3: NSCLC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent
• Males and females age ≥ 18 years
• 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.
• 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).
• Additional Criteria for Phase 2a/Expansion: subjects must have a disease history specific to their disease as listed below:
• 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.
• 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.
• 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.
• One or more measurable tumors lesions per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow, hepatic and renal function.

You may not qualify if:

• Superior vena cava syndrome contra-indicating hydration
• Untreated or symptomatic central nervous system (CNS) metastases
• 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)
• 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.
• Radiation therapy within 2 weeks before first dose of any study treatment or unresolved (NCI CTCAE v5.0 Grade \> 1) toxicity from previous radiotherapy
• Clinically significant cardiovascular disease
• Major surgery within 4 weeks prior to any study treatment administration
• 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
• Active uncontrolled viral, fungal, or bacterial infection requiring systematic therapy within 14 days prior to first dose of study treatment.
• 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.
• Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring systemic immunosuppressive therapy
• A serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
• Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study

Sponsors & Collaborators

• NKGen Biotech, Inc.: lead
• Affimed GmbH: collaborator

Study Sites (3)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

University of Chicago

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasms; Neoplasm Metastasis; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Paul Chang, MPH

  NKGen Biotech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: October 29, 2021
• Study Start: November 3, 2021
• Primary Completion: September 21, 2023
• Study Completion: September 21, 2023
• Last Updated: March 1, 2024

Record last verified: 2023-07

Locations

US (3)