A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
- Conditions
- Solid Neoplasms
- Registration Number
- JPRN-jRCT2031230532
- Lead Sponsor
- Kimura Akiko
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 368
1.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
2.Dazostinag SA (dose escalation Part 1A):
- With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies.
3.Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japan safety lead-in):
- With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to them, including:
- Tumors that have relapsed or are refractory to anti-programmed cell death ligand protein 1 (anti PD-(L)-1) therapy.
- Tumors that are naive to anti-PD-(L)-1 therapy.
4.For expansion phase only:
- SCCHN (Part 2):
- Participants with histologically confirmed (cytological diagnosis is acceptable) metastatic or recurrent, unresectable SCCHN that is considered incurable by local therapies. Participants should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months before signing consent if given as part of multimodal treatment of locally advanced disease is allowed.
- Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal). The exception to this is nasopharyngeal cancer and salivary gland tumors, which will not be included.
- Participants with oropharyngeal cancer or tumors arising in the paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to provide archival tissue for human papilloma virus (HPV) testing or if known, HPV testing results (using CINtec(R) p16 Histology assay is preferred but not required) and a 70% cutoff point must be provided. Alternatively, archival tissue or a fresh excisional or core needle biopsy (>=2 cores) is required for the determination of HPV status. If HPV status was previously tested using this method (CINtec(R) p16 Histology assay is preferred but not required), no additional testing is required.
- For Part 2A, tumors must have a PD-L1 CPS >=1. Participants must agree to provide fresh tumor biopsy for analysis from a core or excisional biopsy (fine needle aspirate is not sufficient) at screening for PD-L1 CPS assessment by a central laboratory. This specimen may be the diagnostic sample for participants with a new diagnosis of metastatic SCCHN. Participants for whom newly obtained samples cannot be obtained (eg, inaccessible or participant safety concern) may submit an archived specimen only upon agreement from the Sponsor. Archival tissue can be obtained up to 90 days prior to treatment initiation provided there was no other treatment from the time of biopsy until the start of study treatment. For Part 2B, any CPS is eligible but fresh or archival tissue is required for confirmation of CPS status.
- For Part 2B, participants must be eligible to receive treatment with either cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the treating physician.
5.CRC (Part 3):
- Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy with 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at least one line of combination ch
1.Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during the screening period.
2.Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during Cycle 1 Day 1 (C1D1) predose assessment.
3.Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment.
4.Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months.
5.Current history of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade >=2 pleural effusion or ascites not controlled by tap or requiring indwelling catheters.
6.History of brain and leptomeningeal metastasis unless:
- Brain metastases are clinically and radiologically stable or improved (that is, >=6 weeks) following surgery, whole-brain radiation, or stereotactic radiosurgery, AND
- Off corticosteroids.
7.Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.
8.Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).
9.For participants in the dose escalation SA Part 1A only: refusal of standard therapeutic options.
10.For participants receiving pembrolizumab only: contraindication and/or intolerance to the administration of pembrolizumab.
11.For participants receiving chemotherapy in Part 2B: contraindication and/or intolerance to the administration of both platinum agents (cisplatin and carboplatin) and/or 5-FU.
12.Participant has had any other prior or concurrent malignancy within 2 years prior to enrollment with the following exceptions: adequately treated localized basal cell or squamous cell carcinoma, or curatively treated in situ carcinoma of the cervix or breast. Other exceptions may be considered upon sponsor consultation.
13.Concurrent chemotherapy (except for Part 2B), immunotherapy (except for pembrolizumab in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones) unless allowed per exclusion criterion 15.
14.Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.
15.Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 7 days of C1D1 of study drug(s), with the following exceptions:
- Topical, intranasal, inhaled, ocular, intra-articular, and/or other non-systemic corticosteroids.
- Premedications required for computed tomography (CT) or magnetic resonance imaging (MRI) scans.
- Physiological doses of replacement steroid therapy (example: for adrenal insufficiency).
- For participants enrolled in Part 2B, chemotherapy premedication with steroids can be administered according to local standards of care practice.
16.Use of medications that are known clinical organic anion-transporting polypeptide B1 (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method