Osteosarcoma Maintenance Therapy With OST31-164 (OST-164-01)

• ClinicalTrials.gov Identifier: NCT04974008
• Recruitment Status: Completed
• First Posted: July 22, 2021
• Last Update Posted: September 28, 2023
• Sponsor: George Clinical Pty Ltd
• Information provided by (Responsible Party): George Clinical Pty Ltd

Study Description

Brief Summary:

Up to 45 Patients aged 12 to 39 with osteosarcoma (bone cancer) that had recurred in the lungs and has recently been surgically removed will be enrolled. Patients will receive OST31-164 infusions every 3 weeks over 48 weeks and be followed after that for 3 years.

Condition or disease	Intervention/treatment	Phase
Bone Cancer	Drug: OST31-164	Phase 2

Detailed Description:

This is a Phase 2, open-label, multicenter, single-arm study in patients (12-39 years) with a recent history of pulmonary recurrent osteosarcoma that has been completely resected. Planned enrollment is a maximum of 45 patients who will receive OST31-164 as a single agent every 3 weeks for 48 weeks with 4 doses constituting 1 treatment cycle (12 weeks per cycle). Each patient will receive treatment at a dose of 1x109 CFU until week 48 or until disease progression, unacceptable toxicity, or the patient meets any other treatment discontinuation criteria. Following treatment discontinuation, all patients will enter a 3-year survival follow-up period. Exploratory evaluation of immune response will be conducted. If available, tissue from the recent resection will be sent to the COG Biobank for future genomic and pathologic analysis by the COG.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase 2 Study of Maintenance Therapy With OST31-164 After Resection of Recurrent Osteosarcoma
• Actual Study Start Date: October 21, 2021
• Actual Primary Completion Date: September 21, 2023
• Actual Study Completion Date: September 21, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: OST31-164; Patients who will receive OST31-164 as a single agent every 3 weeks for 48 weeks with 4 doses constituting 1 treatment cycle (12 weeks per cycle). Each patient will receive treatment at a dose of 1x109 CFU until week 48 or until disease progression, unacceptable toxicity, or the patient meets any other treatment discontinuation criteria.	Drug: OST31-164; Patients who will receive OST31-164 as a single agent every 3 weeks for 48 weeks with 4 doses constituting 1 treatment cycle (12 weeks per cycle). Each patient will receive treatment at a dose of 1x109 CFU until week 48 or until disease progression, unacceptable toxicity, or the patient meets any other treatment discontinuation criteria.

Outcome Measures

Primary Outcome Measures :

1. Event-Free Survival [ Time Frame: Every 3 months, up to one year ]
   The relative proportion of patients experiencing event-free (recurrence-free) survival at 12 months, compared to historical controls. Patients will be e valuated for recurrence every 3 months, consistent with the standard of care.

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: Every 3 months, up to 3 years ]
   Overall survival of patients for three years will be compared to the 3-year overall survival of historical controls. Patients will be followed every 3 months for overall survival for 3 years.

Other Outcome Measures:

1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Throughout the treatment period of 48 weeks, then every 3 months for 3 years ]
   Incidence of Treatment-Emergent Adverse Events as assessed by NCI CTCAE 5.0. Safety will be assessed throughout the treatment period of 48 weeks. Assessments of potential persistence of the vector every 3 months, will continue for an additional 3 years after treatment.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 39 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Note: Patients enrolled on AOST2031 are eligible for enrollment in the present study.

Patients are eligible to be included in the study only if all the following criteria apply:

Age and Weight

1. Between 12 years of age and 39 years of age at the time the Informed Consent/ Assent form is signed.
2. Weight at least 40 kg. Diagnosis
3. Has histologic confirmation of osteosarcoma at diagnosis.

4. Has at least one episode of disease recurrence in the lungs without limitation on the number of episodes of recurrence as long as the following criteria are met:

   1. Surgical resection of all possible sites of suspected pulmonary metastases to achieve a complete remission within 8 weeks prior to study enrollment
   2. Pathological confirmation of osteosarcoma from at least one resected tumor.
   3. Patients will not require radiographic confirmation of complete remission for enrollment. However, a postoperative CT chest scan is required as a baseline for future comparisons.

   https://members.childrensoncologygroup.org/files/Disc/surgery/handbooks/OsteoBoneHandbook.pdf) Performance Status

5. Patient must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky scale for patients > 16 years of age and Lansky scale for patients < years of age Prior Therapy

6. Patient must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, radiotherapy, or surgery prior to entering this study.

   Organ Function Requirements

7. Patient has adequate organ function as defined below:

   a. Hematological: i. Absolute neutrophil count (ANC) is at least 1,000/µL without transfusion or growth factor support. ii. Platelet count ≥ 50,000/µL without transfusion or growth factor support. b. Adequate renal function defined as: i. Creatine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 or ii. A serum creatine based on age/gender as follows:

   Maximum Serum Creatinine (mg/dL)

   Age: 12 to < 13 years Male :1.2 Female:1.2 Age:13 to < 16 years Male :1.5 Female:1.4 Age: ≥ 16 years Male :1.7 Female:1.4 Note: the threshold for creatinine values in this table were derived from the Schwartz formula for estimating GFR.

   c. Adequate liver function defined as: i. Total bilirubin < 1.5 x upper limit of normal (ULN) for age ii. Serum glutamic-pyruvic transaminase (SGPT) / alanine aminotransferase (ALT) < 110 U/L (for the purpose of this study the ULN for SGPT is 45 U/L) iii. Serum albumin > 2 g/dL

   d. Adequate coagulation i. International normalized ratio (INR) or prothrombin time (PT) < 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or INR is within therapeutic range of intended use of anticoagulants.

   ii. Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless patient is receiving anticoagulant therapy as long as aPTT is within therapeutic range of intended use of anticoagulants.

   e. Adequate cardiac function defined as: i. Shortening fraction of > 27% by echocardiogram, or ii. Ejection fraction of > 50% by radionuclide angiogram or echocardiogram f. Adequate pulmonary function defined as: i. No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse oximetry of > 94%.

   g. Central nervous system (CNS) function defined as: i. Patients with a known seizure disorder may be enrolled if on anticonvulsants and/or are well-controlled.

   ii. CNS toxicity including peripheral neuropathy < Grade 2.

8. Patient and/or patient's parent or legal guardian must be capable of understanding the investigational nature, potential risks, and benefits of the study. The patient and/or the parent or legal guardian must sign a written informed consent. Age-appropriate assent will be obtained per institutional guidelines.

   Contraception:

   Female patients :

9. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP) as defined in the protocol OR
   2. A WOCBP who agrees to follow the contraceptive guidance in the protocol during the treatment period and for at least 120 days after the last dose of study treatment.

10. A female patient of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving any dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

    Male patients:

11. A male patient is eligible to participate if he agrees to follow the contraceptive guidance in the protocol during the study treatment period and for at least 120 days after the last dose of study treatment.

Exclusion Criteria:

1. Has clinically evident metastatic or recurrent disease.
2. Has concurrent pulmonary recurrence and local recurrence at the primary tumor site.
3. Has primary refractory disease with progression of the primary tumor on initial-therapy.
4. Has CNS or any extrapulmonary disease involvement at the time of the most recent episode of disease recurrence proceeding enrollment.
5. Has active infection requiring systemic therapy or is dependent on or is currently receiving systemic antibiotics that cannot be discontinued before dosing. (Note: Patients who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any OST31-164 infusion). Inhaled prophylactic PJP (pneumocystis jiroveci pneumonia) treatment is acceptable per Investigator discretion.
6. Is currently dependent on or has received corticosteroids within the past 4 weeks (topical corticosteroids and occasional inhaled corticosteroids are allowed).
7. Is currently participating in or has participated in a study of an investigational agent or is using an investigational device within 4 weeks of the first dose of treatment.
8. Has a history of other active malignancy for < 2 years prior to enrollment. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy or is felt by the Investigator to be at low risk for recurrence is allowed.
9. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
10. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
11. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
12. Has a known allergy to any component of the study treatment(s) formulations.
13. Has a contraindication (e.g., sensitivity/allergy) to both trimethoprim/ sulfamethoxazole and amoxicillin.
14. Has contraindication to administration of NSAIDs.
15. Is currently receiving or will be receiving any chemotherapy, including PI3K inhibitors, during the treatment phase.
16. Has had a prior monoclonal antibody therapy within 2 weeks prior to study Day 1.
17. Requires or anticipates requiring tumor necrosis factor (TNF) blocking agent (e.g., infliximab) therapy for diagnosis of rheumatologic disease or inflammatory bowel disease (e.g., ankylosing spondylitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, or ulcerative colitis).
18. Has previous history of listeriosis.
19. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
20. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected).
21. Has received a live vaccine within 30 days prior to Study Day 1.
22. Patient is or has an immediate family member (spouse, children, or parent) who is directly involved with this study or is employed by the investigational site or Sponsor, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific patient.

Regulatory Requirements:

1. All patients and/or their parents or legal guardians must sign a written informed consent.
2. All institutional, FDA, and NCI requirements for human studies must be met.

Contacts and Locations

Locations

United States, California

Kaiser Permanente Downey Medical Center

Los Angeles, California, United States, 90027

Children's Hospital of Orange County

Orange, California, United States, 92057

Rady Children's Hospital

San Diego, California, United States, 92123

United States, Colorado

Children's Hospital of Colorado

Aurora, Colorado, United States, 80045

United States, Connecticut

Connecticut Children's

Hartford, Connecticut, United States, 06106

United States, Delaware

Nemours/ Alfred I duPont Hospital for Children

Wilmington, Delaware, United States, 19803

United States, Florida

Johns Hopkins All Children's Hospital

Saint Petersburg, Florida, United States, 33701

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30322

United States, Illinois

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60611

United States, Maryland

Johns Hopkins Medical Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Minnesota

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States, 55455

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98101

Sponsors and Collaborators

George Clinical Pty Ltd

Investigators

• Study Director: Robert Petit, PhD; OS Therapies, Inc.

More Information

• Responsible Party: George Clinical Pty Ltd
• ClinicalTrials.gov Identifier: NCT04974008
• Other Study ID Numbers: OST31-164-01 (AOST2121)
• First Posted: July 22, 2021
• Last Update Posted: September 28, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by George Clinical Pty Ltd:

Osteosarcoma; Bone Cancer

Additional relevant MeSH terms:

Osteosarcoma; Bone Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases