NCT04552704

CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study

Terminated Phase 1, PHASE2 Results posted Last updated 2 August 2023

What this trial tests

Phase 1, PHASE2 trial testing CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc in Advanced Malignant Solid Neoplasm in 3 participants. Terminated before completion.

Timeline

30 October 2020

Primary endpoint
3 February 2021

26 January 2022

Quick facts

Lead sponsor	Tianhong Li
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	3
Start date	30 October 2020
Primary completion	3 February 2021
Estimated completion	26 January 2022
Sites	1 location across United States

Drugs / interventions tested

• CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc — full drug profile →
• Placebo Administration — full drug profile →

Conditions studied

• Advanced Malignant Solid Neoplasm — all drugs for Advanced Malignant Solid Neoplasm →

Sponsor

Tianhong Li — full company profile →

Who can join

18 and older, any sex, with Advanced Malignant Solid Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With New Adverse Event (AE) of Grade >= 3 (Phase I) Primary · At day 60

Number of Participants with New Adverse Event (AE) of Grade \>= 3 (Phase I)

Group	Value	95% CI
Phase I	1

Time to irAE Reduction by at Least 1 Grade From the Initiation of CD24Fc Treatment (Phase I) Secondary · Up to 1 year

Time to irAE reduction by at least 1 grade from the initiation of CD24Fc treatment.

Group	Value	95% CI
Phase I	14	14 – 14

Time to All irAEs Reduced to =< 1 From the Initiation of CD24Fc Treatment (Phase I) Secondary · Up to 2 weeks

Time to all irAEs reduced to =\< 1 from the initiation of CD24Fc treatment (Phase I)

Group	Value	95% CI
Phase I	14	14 – 14

Time to Resume Immune Check Point Inhibitor (ICI) Treatment From the Initiation of CD24Fc Treatment (Phase I) Secondary · Up to about 3.5 months

Time to resume immune check point inhibitor (ICI) treatment from the initiation of CD24Fc treatment (Phase I)

Group	Value	95% CI
Phase I	84.5	61 – 108

Recovery Rate (Reduction of irAE by One Grade) (Phase I) Secondary · At day 42

The fraction of patients who experience a partial response (PR) or complete response (CR) will be determined by dividing the number of responders by the total evaluable patients.

Group	Value	95% CI
Phase I	100

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 60 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I

Serious: 1/3 (33%)

Deaths: 1/3

Serious adverse events (5 terms)

Reaction	System	Phase I
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Dysphagia	Gastrointestinal disorders	—
Odynophagia	Gastrointestinal disorders	—
Fever	General disorders	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (34 terms — click to expand)

Reaction	System	Phase I
Blood bicarbonate decreased	Investigations	—
Hyperglycemia	Metabolism and nutrition disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Blood bilirubin increased	Investigations	—
Fatigue	General disorders	—
Hepatic infection	Infections and infestations	—
Hypocalcemia	Metabolism and nutrition disorders	—
Hypokalemia	Metabolism and nutrition disorders	—
Infections and infestations - ascending thoracic aneurysm	Infections and infestations	—
Infections and infestations - BUN decreased	Infections and infestations	—
Infections and infestations - tachypnea	Infections and infestations	—
Lymphocyte count decreased	Investigations	—
Platelet count decreased	Investigations	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—
White blood cell decreased	Investigations	—
Palor	Blood and lymphatic system disorders	—
Diarrhea	Gastrointestinal disorders	—
Heart burn	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Alkaline phosphatase increased	Investigations	—
Elevated neutrophil	Investigations	—
GGT elevated	Investigations	—
WBC elevated	Investigations	—
Anorexia	Metabolism and nutrition disorders	—
New lingular plueral-based opacity with increased FDG	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Possible new segment 2 metastatic lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—
Left vocal chord paralysis	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Dyspnea, Dysphagia, Odynophagia, Fever, Pneumonia.

Data from ClinicalTrials.gov NCT04552704 adverse events section.

Sponsor's own description

This phase I/II trial investigates the side effects and how well CD24Fc works in treating immune related adverse events in patients with solid tumors that have spread to other places in the body (advanced). CD24Fc may prevent autoimmune reactions due to the tissue damage induced by cancer treatment. CD24Fc binds to injured cell components and prevents inflammatory responses. CD24Fc also acts to turn off the immune system after it has been activated ("immune checkpoint"). Adding CD24Fc to standard treatment may shorten the recovery time and reduce the severity of side effects from immunotherapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging phagocytosis checkpoints in cancer immunotherapy.
   Liu Y, Liu Y, Wang Y, Yang Y, et al · · 2023 · cited 186× · PMID 36882399 · DOI 10.1038/s41392-023-01365-z
2. CD24: A Novel Target for Cancer Immunotherapy.
   Panagiotou E, Syrigos NK, Charpidou A, Kotteas E, et al · · 2022 · cited 63× · PMID 36013184 · DOI 10.3390/jpm12081235
3. Targeting CD24/Siglec-10 signal pathway for cancer immunotherapy: recent advances and future directions.
   Li X, Tian W, Jiang Z, Song Y, et al · · 2024 · cited 48× · PMID 38279998 · DOI 10.1007/s00262-023-03606-0
4. Don't eat me/eat me signals as a novel strategy in cancer immunotherapy.
   Khalaji A, Yancheshmeh FB, Farham F, Khorram A, et al · · 2023 · cited 44× · PMID 37822610 · DOI 10.1016/j.heliyon.2023.e20507
5. Targeting CD24 as a novel immunotherapy for solid cancers.
   Yang Y, Zhu G, Yang L, Yang Y. · · 2023 · cited 37× · PMID 37919766 · DOI 10.1186/s12964-023-01315-w
6. Steroid-Refractory Immune-Related Adverse Events Induced by Checkpoint Inhibitors.
   Tomsitz D, Ruf T, Zierold S, French LE, et al · · 2023 · cited 26× · PMID 37174003 · DOI 10.3390/cancers15092538
7. IMM47, a humanized monoclonal antibody that targets CD24, exhibits exceptional anti-tumor efficacy by blocking the CD24/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy.
   Li S, Chen D, Guo H, Yang Y, et al · · 2023 · cited 15× · PMID 37846296 · DOI 10.1093/abt/tbad020
8. TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis.
   Liu X, Wu W, Fang L, Liu Y, et al · · 2022 · cited 15× · PMID 35844550 · DOI 10.3389/fimmu.2022.922782