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Squamous Cell Carcinoma of Head and NeckPhase 1/2NCT05099549

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

A Phase 1/2 study testing AFM24 and SNK01 in people with Squamous Cell Carcinoma of Head and Neck and Carcinoma, Non-Small-Cell Lung, run by NKGen Biotech, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AFM24 and SNK01
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
3 sitesUnited States
Study dates
3 Nov 2021to 21 Sep 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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.

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • University of Chicago

    Chicago, Illinois, 60611

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
AFM24, SNK01
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
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasms, Neoplasm Metastasis, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AFM24Drug

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

  • SNK01Biological

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

Study groups in NCT05099549
Study groupRoleWhat they receive
Phase 1, Dose EscalationExperimentalIt 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.
Receives: Drug: AFM24; Biological: SNK01
Phase 2a, Expansion Cohort 1 - Metastatic colorectal cancer (EXP-1: mCRC)ExperimentalSNK01 (fixed dose) will be administered weekly by IV infusion.
Receives: Drug: AFM24; Biological: SNK01
Phase 2a, Expansion Cohort 2 - Head and Neck Squamous Cell Carcinoma (EXP-2: SCCHN)ExperimentalSNK01 (fixed dose) will be administered weekly by IV infusion.
Receives: Drug: AFM24; Biological: SNK01
Phase 2a, Expansion Cohort 3 - Non-small cell lung cancer (EXP-3: NSCLC)ExperimentalSNK01 (fixed dose) will be administered weekly by IV infusion.
Receives: Drug: AFM24; Biological: SNK01

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days starting on cycle 1 day 1

  2. 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.

    Measured: 28 days starting on cycle 1 day 1

  3. 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

    Measured: Up to 24 months

Secondary outcomes (17)
  1. 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).

    Measured: Up to 24 months

  2. Phase 1/Dose Escalation

    Determine preliminary efficacy of AFM24 in combination with SNK01. Determine ORR using RECIST v1.1 evaluated by local assessment.

    Measured: Up to 24 months

  3. Phase 1/Dose Escalation

    Maximum observed plasma concentration (Cmax) of AFM24

    Measured: 28 days starting on cycle 1 day 1

  4. Phase 1/Dose Escalation

    Time to maximum plasma concentration (Tmax) of AFM24

    Measured: 28 days starting on cycle 1 day 1

  5. Phase 1/Dose Escalation

    Minimum plasma concentration (Cmin) of AFM24

    Measured: 28 days starting on cycle 1 day 1

  6. Phase 1/Dose Escalation

    Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24

    Measured: 28 days starting on cycle 1 day 1

  7. 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

    Measured: Up to 24 months

  8. Phase 2a/Expansion

    Safety and tolerability of AFM24 in combination with SNK01 Frequency of TEAEs graded according to NCI CTCAE v 5.0

    Measured: Up to 24 months

  9. 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.

    Measured: Up to 24 months

  10. Phase 2a/Expansion

    To assess overall survival (OS).

    Measured: Up to 24 months

  11. Phase 2a/Expansion

    To assess duration of response (DOR) according to RECIST v1.1 by local assessment.

    Measured: Up to 24 months

  12. Phase 2a/Expansion

    To assess clinical benefit rate (CBR) according to RECIST v1.1 by local assessment.

    Measured: Up to 24 months

  13. Phase 2a/Expansion

    Maximum observed plasma concentration (Cmax) of AFM24.

    Measured: 28 days starting on cycle 1 day 1

  14. Phase 2a/Expansion

    Time to maximum plasma concentration (Tmax) of AFM24.

    Measured: 28 days starting on cycle 1 day 1

  15. Phase 2a/Expansion

    Minimum plasma concentration (Cmin) of AFM24.

    Measured: 28 days starting on cycle 1 day 1

  16. Phase 2a/Expansion

    Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24.

    Measured: 28 days starting on cycle 1 day 1

  17. 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.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2021
  2. Study start3 Nov 2021
  3. Primary completion21 Sep 2023
  4. Study completion21 Sep 2023

Why it stopped: 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.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05099549
Sponsor's protocol ID
AFM24-SNK01-103
Status last verified
Jul 2023
First submitted
18 Oct 2021
Last updated
1 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AFM24 and SNK01 in people with Squamous Cell Carcinoma of Head and Neck and Carcinoma, Non-Small-Cell Lung, run by NKGen Biotech, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 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.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1/Dose Escalation (time frame: 28 days starting on cycle 1 day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2024.

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