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

NCT04552704 | Terminated Phase 1 Results DMC FDA Drug

• 5 other identifiers: 1626396NCI-2020-05955UCDCC#292P30CA093373CD24Fc-006
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Number of Participants With New Adverse Event (AE) of Grade >= 3 (Phase I)

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

  At day 60

• Recovery Rate (Phase II)

  Defined by reduction of irAE by one grade. Kaplan-Meier plots and confidence intervals will be used to summarize outcomes. Medians and associated 95% confidence intervals will be calculated, and comparisons between groups will be performed by log-rank tests. Cox proportional hazard models will be used to explore association between covariates and outcomes.

  At day 42

• Time to Recovery From Grade 2 or 3 irAE (Phase II)

  Will assess time to recovery from grade 2 or 3 irAE (as defined by reduction of at least 1 grade in irAE severity) from the initiation of CD24Fc treatment. Patients who have not been documented to have event (reduction of at least 1 grade) will be censored at the date of the latest clinical assessment that documented as being free of event.

  Up to 1 year

Secondary Outcomes (9)

• Time to irAE Reduction by at Least 1 Grade From the Initiation of CD24Fc Treatment (Phase I)

  Up to 1 year

• Time to All irAEs Reduced to =< 1 From the Initiation of CD24Fc Treatment (Phase I)

  Up to 2 weeks

• Time to Resume Immune Check Point Inhibitor (ICI) Treatment From the Initiation of CD24Fc Treatment (Phase I)

  Up to about 3.5 months

• Recovery Rate (Reduction of irAE by One Grade) (Phase I)

  At day 42

• Time to All irAEs Reduced to =< 1 From the Initiation of CD24Fc Treatment (Phase II)

  Up to 1 year

Study Arms (3)

Phase I (CD24Fc)

EXPERIMENTAL

Patients receive CD24Fc IV over 60 minutes on days 1, 14, and 28 with standard of care (i.e., steroids per treating physician and best supportive care) in the absence of disease progression or unacceptable toxicity.

Biological: CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc

Phase II, Arm I (CD24Fc)

EXPERIMENTAL

Patients receive CD24Fc IV over 60 minutes on days 1, 14, and 28 in addition to standard of care treatment for irAE in the absence of disease progression or unacceptable toxicity.

Biological: CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc

Phase II, Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo IV over 60 minutes on days 1, 14, and 28 in addition to standard of care treatment for irAE in the absence of disease progression or unacceptable toxicity.

Drug: Placebo Administration

Interventions

CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc BIOLOGICAL

Given IV

Also known as: CD24Fc, CD24Fc CD24IgG

Phase I (CD24Fc); Phase II, Arm I (CD24Fc)

Placebo Administration DRUG

Given IV

Phase II, Arm II (placebo)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and willingness to sign an informed consent form
• At least 18 years of age
• Histologically confirmed advanced solid tumors
• Patients must have grade 2 or 3 irAEs from at least one ICI-containing regimen. Both newly emerging and persistent irAEs are allowed. Systemic steroid therapy or any other form of immunosuppressive therapy for irAEs is allowed. The specific irAEs are
• Grade 2-3 diarrhea/colitis: Patients with \>= 4 stools per day or moderate-severe increase in ostomy output compared to baseline but not life-threatening diarrhea
• Grade 2-3 pneumonitis: Mild to moderate (grade 2) or severe (grade 3) symptoms (including hypoxia, shortness of breath, requiring oxygen) but not life-threatening respiratory compromise requiring urgent intervention (e.g., tracheostomy or intubation)
• Grade 2-3 renal irAE: Creatine increased between 1.6-6.0 x upper limit of normal (ULN) or =\< 3.0 x baseline if baseline was abnormal, estimated glomerular filtration rate (eGFR) or creatinine clearance \>= 15 ml/min/1.73m\^2 but not life-threatening consequences or requiring dialysis
• Grade 2-3 Hepatic irAE: AST/ALT/ALP levels 3-20 x ULN, and T bilirubin increased \<5 x ULN
• Grade 2-3 skin rash: moderate (10-30% body surface area, BSA) to severe (\> 30% BSA) but not life-threatening skin lesions or Stevens-Johnson syndrome
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Life expectancy of \>= 3 months at the time of enrollment
• Pretreatment absolute neutrophil count (ANC) \>= 1,000/uL obtained within 14 days prior to 1st dose of treatment
• Pretreatment hemoglobin \>= 8 gm/dL obtained within 14 days prior to 1st dose of treatment
• Pretreatment platelet count of \>= 75,000/uL obtained within 14 days prior to 1st dose of treatment
• Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for \>= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Or, female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration

You may not qualify if:

• Prior CD24Fc therapy
• Any known active hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, including patients who have an active infection requiring systemic therapy. History of COVID-19 or known asymptomatic carrier of SARS-CoV-2 virus is allowed
• Pregnant or lactating women
• Any medical condition including additional laboratory abnormalities, or psychiatric illness that would, in the opinion of the investigator, prevent the subject from participating and adhering to study related procedures
• Any known severe bacterial, fungal, or viral infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 2 weeks prior to enrollment
• Patients with concomitant proarrhythmic medications
• Patients with heart failure in New York (NY) Heart Association stage IV
• Any grade 4 irAE symptoms and Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 grade 4 toxicity
• AST, ALT, gamma glutamyl transpeptidase (GGT), or ALP \> 20.0 x ULN regardless of baseline
• Blood bilirubin \>5.0 x ULN regardless of baseline
• Creatinine \> 6.0 x ULN or creatinine clearance \<15 ml/min/1.73m2
• Urine: Anuria \< 140 ml in 24 hours
• Electrolytes hyponatremia, sodium \< 120 mmol/L
• Hypokalemia, potassium \< 2.5 mmol/L
• Creatine kinase (CPK) \> 10.0 ULN

Sponsors & Collaborators

• Tianhong Li: lead
• National Cancer Institute (NCI): collaborator
• Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Limitations and Caveats

The study was terminated by the sponsor after 3 out of 6 patients enrolled in phase I study.

Results Point of Contact

• Title: Analyst
• Organization: University of California, Davis

nlogihara@ucdavis.edu

916-734-8053

Study Officials

• Tianhong Li

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 17, 2020
• Study Start: October 30, 2020
• Primary Completion: February 3, 2021
• Study Completion: January 26, 2022
• Last Updated: August 2, 2023
• Results First Posted: April 4, 2022

Record last verified: 2023-08

Locations

US (1)