Advanced HER2-Expressing Solid Tumors MedDRA version: 23.0 Level: PT Classification code 10075638 Term: HER2 protein overexpression System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 23.0 Level: PT Classification code 10075653 Term: HER2 gene amplification System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BDC-1001
Product Code: [BDC-1001]
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: TLR7/8
Current Sponsor code: A00104
Concentration unit: µg microgram(s
Sponsors
Bolt Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.For P.1 and P.2: a.Pt has an advanced solid tumor for which approved therapies have been exhausted or for which the Investigator considers the patient ineligible or intolerant of other forms of treatment bTumor has documented HER2 expression. At least 1 of the first 3 patients evaluated for DLT in Cohort M2 and all subsequent cohorts in Part 1 requires documented HER2 protein expression in tumor tissue. 2.For Part 3 and Part 4: a.Patient has an advanced solid tumor for which approved therapies have been exhausted or for which the Investigator considers the patient ineligible or intolerant of other forms of treatment and also has the following: breast cancer HER2+ cohorts (3A and 4A): 1)Has histologically documented advanced or metastatic HER2+ breast cancer 2)Has received at least 2 prior treatment regimens with anti-HER2 agents For GE cancer cohorts (3B and 4B): 1)Has histologically documented advanced or metastatic HER2+ GE cancer 2)Has prior treatment with trastuzumab based therapy For other tumor types cohorts (3C and 4C): 1)Has histologically documented advanced or metastatic HER2+ cancer other than CRC, endometrial cancer, GE cancer, or breast cancer For HER2-low breast cancer cohorts (3D and 4D) 1)Has histologically documented advanced or metastatic breast cancer 2)HER2-low tumors are defined as IHC2+ and negative or equivocal gene amplification For CRC with HER2+ tumor cohorts (3E and 4E) 1)Has histologically documented advanced or metastatic HER2+ CRC For endometrial cancer with HER2+ tumor cohorts (3F and 4F) 1)Has histologically documented advanced or metastatic HER2+ endometrial cancer 3.Age greater than or equal to 18 years old 4.Mentally competent and able to understand and sign the informed consent form 5.Eastern Cooperative Oncology Group performance status of 0 or 1 6.Expected life expectancy of greater than 12 weeks. 7.Has LVEF = 50% by either echocardiography or multiple-gated acquisition within 28 days before C1D1 8.Has disease that is measurable by (RECIST) v1.1 9.Has tumor tissue (archival or collected prior to the study start) available for exploratory biomarker evaluation. A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or at least 15 unstained, freshly cut, serial sections (on slides) from an FFPE tumor specimen is required for participation in this study. The specimen must be accompanied by the associated pathology report. a.If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with the Medical Monitor if the patient is willing to consent to and undergo a pretreatment tumor biopsy collection. b.The following specimen types are acceptable: resections, core needle biopsies, excisional, incisional, punch, or forceps biopsies. For core needle biopsy specimens, preferably, at least 3 cores embedded in a single paraffin block should be submitted for evaluation. For all specimen types, submitted blocks should have sufficient tissue to generate at least 15 sections, and each section should contain at least 100 viable tumor cells. c.Fine-needle aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension and/or cell smears), brushing, cell pellet from pleural effusion, and lavage samples are not acceptable. d.Tumor tissue from bone metastases that have been decalcified is not acceptable. 10.Willing and able to provide blood samples prior to the start of this study. 11.At lea
Exclusion criteria
Exclusion criteria: 1.For Part 2 and Part 4 with BDC 1001 and nivolumab combination therapy: a.Patient has a history of immune-mediated colitis b.Patient has an active autoimmune disease with the exception of autoimmune endocrinopathies that are stable on hormone replacement therapy c.History of allergy or hypersensitivity to nivolumab components d.History of life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4 or anti-PD-1/ PD L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, Hypothyroidism) 2.Cardiovascular exclusions: a.Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II IV) or a cardiac arrhythmia that requires treatment b.Has a medical history of myocardial infarction or unstable angina within 6 months before C1D1 c.Has a mean QTcF prolongation of > 450 milliseconds (ms) in males and > 470 ms in females based on a 12 lead electrocardiogram (ECG) in triplicate d.Has a medical history of an arterial thrombotic event, stroke, or transient ischemia attack within the past 12 months 3.Other exclusions: a.History of treatment with a toll-like receptor (TLR)7, TLR8, or TLR7/8 agonist b.Patient was previously enrolled in this study c.Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study d.Use of another investigational agent or anticancer therapy within 4 weeks prior to C1D1 or within 5 estimated elimination half-lives, whichever is shorter e.Treatment with complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks prior to first study treatment. f.Use of another anti-HER2 therapy within 4 weeks prior to C1D1 g.Use of strong inducers or inhibitors of major human cytochrome P450 (CYP) isoenzymes and transporters within 2 weeks prior to C1D1 h.History of severe hypersensitivity to any ingredient of BDC-1001, including trastuzumab. i.Recent medical concerns and exclusions: i.Patient has evidence of active infection and is being treated with intravenous (IV) therapy within 7 days prior to C1D1 ii.Radiation therapy within 2 weeks of C1D1 iii.Patient has active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to C1D1 iv.Patient has an infected wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to C1D1 v.Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to C1D1 vi.Patient has had a live/attenuated virus vaccine within 30 days prior to C1D1 vii.Active SARS-CoV-2 infection as determined by viral testing. viii.Prior history of pneumonitis (contact Medical Monitor) 4.Patient has known human immunodeficiency virus (HIV) infection (by antibody test), active hepatitis B infection (by hepatitis B surface antigen [HbsAg] test), or hepatitis C infection (by antibody test followed by confirmatory RNA test if antibody test is positive) 5.Patient is unwilling to use adequate contraceptive methods (as per Inclusion Section 4.1) 6.Patient has untreated central nervous system or brain metastasis 7.Patient taking steroids exceeding 10 mg/day prednisone for a corticosteroids or equivalent dose. Inhaled, intranasal, intraocular, topical, and intraarticular joint injections of corticosteroids are allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation (Part 1 & 2): Define the safety and tolerability of BDC 1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors. Determine the RP2D for BDC 1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors. Dose Expansion (Parts 3 & 4): Evaluate preliminary antitumor activity of BDC 1001 as monotherapy (Part 3) and in combination with nivolumab (Part 4) in patients with advanced HER2-expressing solid tumors. All: Evaluate exploratory pharmacodynamic biomarkers of BDC 1001 biological activity as monotherapy (Parts 1 and 3) or in combination with nivolumab (Parts 2 and 4) in tumor tissue and peripheral blood in patients with advanced HER2-expressing solid tumors. Explore potential baseline biomarkers associated with BDC 1001 biological activity as monotherapy (Parts 1 and 3) or in combination with nivolumab (Parts 2 and 4).;Secondary Objective: Dose Escalation (Part 1 & 2): Part 1: To analyze PK characteristics of BDC 1001 in patients with advanced HER2 expressing solid tumors. To evaluate preliminary antitumor activity of BDC 1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors. To evaluate the immunogenicity of BDC 1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors. Dose Expansion (Parts 3 & 4): To define the safety and tolerability of BDC 1001 as monotherapy (Part 3) and in combination with nivolumab (Part 4) in patients with advanced HER2-expressing solid tumors. To verify the exposure of BDC 1001. To evaluate the immunogenicity of BDC 1001 as monotherapy (Part 3) or in combination with nivolumab (Part 4) in patients with advanced HER2-expressing solid tumors.;Primary end point(s): Dose Escalation (Part 1 and Part 2): •Incidence of AEs and SAEs graded acco | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Related to Parts 1, 2, 3, and 4. | — |
Countries
Italy, Korea, Republic of, United States
Contacts
Public ContactJonathan Harris
Bolt Biotherapeutics, Inc.
Outcome results
None listed