BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours

• ClinicalTrials.gov Identifier: NCT04421820
• Recruitment Status: Recruiting
• First Posted: June 9, 2020
• Last Update Posted: March 23, 2023
• Sponsor: Bold Therapeutics, Inc.
• Information provided by (Responsible Party): Bold Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 26, 2020
• First Posted Date: June 9, 2020
• Last Update Posted Date: March 23, 2023
• Actual Study Start Date: August 28, 2020
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 4, 2020)

• Incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions; [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Incidence of dose-limiting toxicities (DLT) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results (chemistry, hematology, coagulation, urinalysis), Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 4, 2020)

• Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Standard PK parameters including Cmin [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Baseline GRP78 biomarker levels (Counts/mL) [ Time Frame: Baseline ]
• Changes in GRP78 biomarker levels during treatment (Counts/mL) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Standard PK parameters including Cmax [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Standard PK parameters including TSS [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Standard PK parameters including CSS [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
• Standard PK parameters including Vdss [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours
• Official Title: A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
• Brief Summary: BOLD-100 is an intravenously administered sterile solution containing the ruthenium-based small molecule. BOLD-100 has been shown to preferentially decrease the expression of GRP78 in tumour cells and ER stressed cells when compared to normal cells. BOLD-100 will be combined with cytotoxic FOLFOX chemotherapy in this study, with a dose escalation cohort to ensure tolerability and safety, followed by a cohort expansion phase.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Pancreatic Cancer
• Gastric Cancers
• Cholangiocarcinoma

Intervention

• Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
  625 mg/m2 IV over 30 minutes, q2weeks
• Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
  320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks

Study Arms

• Experimental: Part B - Dose Expansion - 1L Gastric Cancer (ARM I)
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part B - Dose Expansion - 2L Gastric Cancer (ARM II)
  Open to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III)
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV)
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI)
  Open to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V)
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
• Experimental: Part A - Dose Escalation - Gastric Cancer
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
• Experimental: Part A - Dose Escalation - Pancreatic Cancer
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
• Experimental: Part A - Dose Escalation - Colorectal Cancer
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
• Experimental: Part A - Dose Escalation - Cholangiocarcinoma
  Arm closed to enrollment.
  Intervention: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 7, 2022): 100
• Original Estimated Enrollment (submitted: June 4, 2020): 80
• Estimated Study Completion Date: September 30, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Be 18 years or older.
2. Be male or non-pregnant females who agree to comply with applicable contraceptive requirements of the protocol (see Table 12. Acceptable Contraceptive Methods.)
3. Histologically and/or cytologically confirmed gastrointestinal tumours that are metastatic or unresectable, and are subject to receive FOLFOX as SOC per investigator's judgement. Participants will have received at least one line of chemotherapy in the metastatic setting. Colorectal cancer: Patients must have received at least 1 prior line of therapy prior to enrollment in this study. Pancreatic cancer: Patients must have received at least 1 prior line of therapy. Gastric cancer: Patients who have not received prior treatment may be included in this study. GEJ (gastroesophageal junction) cancer patients are considered eligible to enter this trial. Cholangiocarcinoma: locally advanced or metastatic biliary tract cancer (intra or extrahepatic cholangiocarcinoma or gallbladder cancer) are eligible to enter this trial. Patients must have received at least 1 prior line of therapy (with gemcitabine-based chemotherapy). Colorectal cancer (ARM VI): Patients must have received at least 2 prior lines of therapy prior to enrollment in this study, one of which was a 5-FU based regimen.
4. Have measurable disease according to RECIST v1.1 (at least one measurable lesion).
5. Have an anticipated survival of at least 16 weeks.
6. Be ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.

7. Have adequate organ function, defined as:

   1. Hematologic: ANC ≥ 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count ≥ 100 x 109/L
   2. Hepatic: total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for subjects with Gilbert's Syndrome); transaminases ≤ 2.5 x ULN (may be up to ≤ 5x ULN if clearly due to liver metastases) and ALP ≤ 2.5 x ULN (or ≤ 3 x ULN if liver metastases).
   3. Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min.

   c. Urine protein is 0, trace, or +1 on dipstick urinalysis, or < 1.0 gram on 24-hour urine protein analysis

8. Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion (e.g., non-steroidal anti-inflammatory drugs, corticosteroids, barbiturates, diphenylhydantoin, narcotic analgesics, probenecid). Such drugs should not be initiated while the subject is participating in this study or have been initiated within 30 days beforehand before the start of treatment. Whenever possible, narcotic analgesic doses should be stable within 30 days prior to study entry and during the first cycle of therapy.
9. Resolved acute effects of any prior therapy before the start of treatment to baseline severity or grade ≤1 CTCAE 5.0 except for adverse events not constituting a safety risk by investigator judgment (such as alopecia)
10. Able to take oral medications (for pre-medications and supportive management)
11. Understand and be able, willing, and likely to fully comply with study procedures and restrictions.
12. Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF).

Exclusion Criteria:

1. Neuropathy > grade 2
2. Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin
3. Cerebrovascular accident within the past 6 months before the start of treatment.
4. History or presence of central nervous system (CNS) metastasis or leptomeningeal tumours as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.
5. Any serious medical conditions that might be aggravated by treatment or limit compliance. This includes, but is not limited to uncontrolled psychiatric disorders, serious infections, active peptic ulcer disease and bleeding diathesis

6. Any history of serious cardiac illness including (but not confined to):

   • Previous or active myocardial infarction < 6 months before the start of treatment
   • Congestive cardiac failure (NYHA III or IV)
   • History of unstable angina pectoris < 6 months before the start of treatment
   • Recent coronary artery bypass grafting < 6 months before the start of treatment
   • Uncontrolled hypertension (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg)
   • Ventricular arrhythmia < 6 months before the start of treatment
   • Left ventricular ejection fraction (LVEF) < 50% as measured either by radionuclide angiography or echocardiogram
   • QTc interval > 470 msec
7. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months before the start of treatment
8. Any other known malignancy within 3 years before the start of treatment (with the exception of non-melanoma skin cancer that had undergone curative treatment, cervical cancer in situ, or ductal/lobular carcinoma in situ of the breast that has underwent local treatment
9. Active gastrointestinal tract disease with malabsorption syndrome.
10. Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
11. Treatment with radiation therapy or surgery within 4 weeks prior to starting treatment.
12. Recent history of weight loss > 10% of current body weight in past 3 months before the start of treatment.
13. Current (within 1 week of the start of the study) or regular use of any medication (including OTC, herbal or homeopathic preparations) that could affect (improve or worsen) the cancer being studied, or could affect the action or disposition of BOLD-100, or its clinical or laboratory assessment, e.g., Coumadin therapy, due to high competitive protein binding.
14. HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
15. Any condition potentially decreasing compliance to study procedures. Concurrent use of another investigational therapy or anti-cancer therapy.
16. Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michelle Jones; 604-262-9899; clinical@bold-therapeutics.com

Contact: Jim Pankovich; 604-262-9934; jp@bold-therapeutics.com

• Listed Location Countries: Canada, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT04421820
• Other Study ID Numbers: BOLD-100-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Bold Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Bold Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bold Therapeutics, Inc.
• Verification Date: February 2023