Safety, Tolerability, and Anti-Tumor Activity of AFM24 in Combination With SNK01 in Subjects With Advanced/Metastatic EGFR-Expressing Cancers
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ClinicalTrials.gov Identifier: NCT05099549 |
Recruitment Status :
Terminated
(Affimed and NKGen have mutually decided to discontinue the study. Affimed will evaluate the best options to advance this project with an allogeneic off-the-shelf NK cell product while NKGen will focus on CNS with SNK01.)
First Posted : October 29, 2021
Last Update Posted : March 1, 2024
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Condition or disease | Intervention/treatment | Phase |
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Squamous Cell Carcinoma of Head and Neck Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Advanced Solid Tumor Refractory Tumor Metastatic Tumor | Drug: AFM24 Biological: SNK01 | Phase 1 Phase 2 |
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 (Clinical Trial) |
Actual Enrollment : | 11 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
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. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | November 3, 2021 |
Actual Primary Completion Date : | September 21, 2023 |
Actual Study Completion Date : | September 21, 2023 |
Arm | Intervention/treatment |
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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.
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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.
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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. |
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]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.
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]
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.
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]Determine objective response rate (ORR) of AFM24 in combination with SNK01. Determine ORR using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
- Phase 1/Dose Escalation [ Time Frame: Up to 24 months ]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).
- Phase 1/Dose Escalation [ Time Frame: Up to 24 months ]Determine preliminary efficacy of AFM24 in combination with SNK01. Determine ORR using RECIST v1.1 evaluated by local assessment.
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]Maximum observed plasma concentration (Cmax) of AFM24
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]Time to maximum plasma concentration (Tmax) of AFM24
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]Minimum plasma concentration (Cmin) of AFM24
- Phase 1/Dose Escalation [ Time Frame: 28 days starting on cycle 1 day 1 ]Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24
- Phase 1/Dose Escalation [ Time Frame: Up to 24 months ]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
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]Safety and tolerability of AFM24 in combination with SNK01 Frequency of TEAEs graded according to NCI CTCAE v 5.0
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]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.
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]To assess overall survival (OS).
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]To assess duration of response (DOR) according to RECIST v1.1 by local assessment.
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]To assess clinical benefit rate (CBR) according to RECIST v1.1 by local assessment.
- Phase 2a/Expansion [ Time Frame: 28 days starting on cycle 1 day 1 ]Maximum observed plasma concentration (Cmax) of AFM24.
- Phase 2a/Expansion [ Time Frame: 28 days starting on cycle 1 day 1 ]Time to maximum plasma concentration (Tmax) of AFM24.
- Phase 2a/Expansion [ Time Frame: 28 days starting on cycle 1 day 1 ]Minimum plasma concentration (Cmin) of AFM24.
- Phase 2a/Expansion [ Time Frame: 28 days starting on cycle 1 day 1 ]Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24.
- Phase 2a/Expansion [ Time Frame: Up to 24 months ]Immunogenicity of AFM24 when AFM24 is given in combination with SNK01 Frequency of subjects developing AFM24 ADAs and frequency of subjects developing neutralizing ADAs.
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- 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).
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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.
Key Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05099549
United States, California | |
USC/Norris Comprehensive Cancer Center | |
Los Angeles, California, United States, 90033 | |
Sarcoma Oncology Center | |
Santa Monica, California, United States, 90403 | |
United States, Illinois | |
University of Chicago | |
Chicago, Illinois, United States, 60611 |
Study Director: | Paul Chang, MPH | NKGen Biotech, Inc. |
Responsible Party: | NKGen Biotech, Inc. |
ClinicalTrials.gov Identifier: | NCT05099549 |
Other Study ID Numbers: |
AFM24-SNK01-103 |
First Posted: | October 29, 2021 Key Record Dates |
Last Update Posted: | March 1, 2024 |
Last Verified: | July 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
EGFR Positive EGFR EGFR+ AFM24 SNK01 Solid tumor Lung cancer Refractory Metastatic |
NSCLC SCCHN NK cells Natural killer cell IgG1 antibody CD16A ADCC ADCP |
Carcinoma Neoplasms Colorectal Neoplasms Carcinoma, Non-Small-Cell Lung Squamous Cell Carcinoma of Head and Neck Neoplasm Metastasis Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Carcinoma, Squamous Cell Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases |
Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Head and Neck Neoplasms Neoplastic Processes Pathologic Processes |