A Study in Subjects With Advanced Solid Tumors

NCT04156100 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: C-900-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and pharmacodynamic profiles of AGEN1223 as a single-agent and in combination with balstilimab, as well as to assess the maximum tolerated dose and determine the RP2D of AGEN1223 as a single-agent and in combination with balstilimab in subjects with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Cancer, Solid Tumor, PD-L1

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  In subjects in dose escalation

  First 28 days of treatment

• Frequency, severity, and duration of treatment-emergent AEs (TEAEs)

  For all dose groups according to NCI-CTCAE Version 5.0

  Screening through 90 days after last dose

Secondary Outcomes (15)

• Maximum observed concentration at steady state (Cmax-ss)

  From first dose through 2 year of treatment

• Minimum observed concentration at steady state (Cmin-ss)

  From first dose through 2 year of treatment

• Area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)

  From first dose through 2 year of treatment

• Area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))

  From first dose through 2 year of treatment

• Area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))

  From first dose through 2 year of treatment

Other Outcomes (5)

• PK parameter correlation to pharmacodynamic assessments

  Screening up to 1 year of treatment

• Characterization of genetic polymorphism of FcyR

  Screening up to 2 years of treatment

• Biomarkers of pharmacologic activity

  Screening up to 1 year of treatment

Study Arms (2)

AGEN1223

EXPERIMENTAL

AGEN1223 is a bispecific antibody.

Drug: AGEN1223

AGEN1223 and balstilimab

EXPERIMENTAL

AGEN1223 is a bispecific antibody and balstilimab an anti-PD-1 Monoclonal Antibody

Drug: AGEN1223 and balstilimab

Interventions

AGEN1223 DRUG

AGEN1223 is a bispecific antibody.

AGEN1223

AGEN1223 and balstilimab DRUG

AGEN1223 is a bispecific antibody and balstilimab an anti-PD-1 Monoclonal Antibody.

AGEN1223 and balstilimab

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures (participation in genetic testing is optional).
• Greater than or equal to 18 years of age
• Histologically or cytologically confirmed diagnosis of an advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• Measurable disease on baseline imaging based on RECIST 1.1.
• Life expectancy of at least 3 months and an ECOG performance status of 0 or 1 (Appendix A).
• Adequate organ function as indicated by the following laboratory values:
• Adequate hematological function, defined as ANC ≥1.5 × 109/L, platelet count ≥100 × 109/L, and hemoglobin ≥8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement).
• Adequate hepatic function based by a total bilirubin level ≤1.5 × the institutional upper limit of normal (IULN), AST level ≤2.5 × IULN, ALT level ≤2.5 × IULN.
• Adequate renal function defined as creatinine ≤1.5 × IULN or measured or calculated creatinine clearance \>40 mL/min per institutional standard. Assessment methods should be recorded.
• Adequate coagulation defined by international normalized ratio or prothrombin time ≤1.5 × IULN and activated partial thromboplastin time ≤1.5 × IULN (unless the subject is receiving anticoagulant therapy).
• No history of prior or concomitant malignancy that requires other active treatment.
• Subjects must provide a sufficient and adequate FFPE tumor tissue sample (fresh biopsy) collected within 28 days before the first dose from a site not previously irradiated and to agree to a mandatory on-treatment biopsy if clinically feasible.
• Female subjects of child-bearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Subjects with tumors producing human chorionic gonadotropin and gestational trophoblastic tumor do not need a serum pregnancy test, and absence of pregnancy should be documented by the Principal Investigator (PI) based on clinical and radiological assessments as needed. Non-childbearing potential is defined as:
• ≥45 years of age and has not had menses for greater than 1 year,
• Amenorrheic for ≥2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon prestudy (screening) evaluation,

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of the first dose of current study drug.
• Any relevant bispecific antibody, and/or anti-PD-1/PDL1 agents. For selected indication cohorts, prior treatment may be permitted after discussion with the Sponsor. Prior therapy with PD-1/PDL1 inhibitor may be allowed in agreement with the Sponsor.
• Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study drug; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with Sponsor approval.
• Persisting toxicity with Grade \>1 severity related to prior therapy based on NCI-CTCAE Version 5.0.
• Note: Sensory neuropathy and alopecia of Grade ≤2 are acceptable.
• Expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
• Known severe hypersensitivity reactions (NCI-CTCAE Grade ≥3) to fully human monoclonal antibodies, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis, requiring treatment with steroids, or has a history of interstitial lung disease (ILD), any history of anaphylaxis, or uncontrolled asthma.
• Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication.
• Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Subjects who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of up to 7.5 mg or equivalent hydrocortisone doses are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted.
• CNS tumor, metastasis, and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period or identified prior to consent.
• Note: Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (defined as 2 brain images, both of which are obtained after treatment to the brain metastases; these imaging scans should both be obtained ≥4 weeks apart). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed ≥3 days prior to the first dose of study medication.
• Active or history of autoimmune disease that has required systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Note: Subjects with diabetes type 1, vitiligo, psoriasis, and hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Allogeneic tissue/solid organ transplant, except those not requiring immuno-suppressive treatment.
• Active infection requiring treatment.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (4)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Miami/Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Abramson Cancer Center at the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

balstilimab

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: November 7, 2019
• Study Start: December 10, 2019
• Primary Completion: April 8, 2021
• Study Completion: September 29, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)