First-in-human (FIH) study of DRP-104 as single agent and in combination with atezolizumab in patients with advanced solid tumors.
- Conditions
- Cancer, advanced solid tumorsMedDRA version: 21.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002770-27-DE
- Lead Sponsor
- Dracen Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 170
• Signed Informed Consent Form.
• Male or female, 18 years of age or older.
• Target Population - all patients regardless of study part:
o Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable.
o Patients must have measurable disease per RECIST 1.1 (Eisenhauer et al., 2009; Schwartz et al., 2016) with the exception of castration-resistant prostate cancer (CRPC) who should have progression based on the PCWG 3.0 criteria (Scher et al., 2016). Lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
o At time of enrollment, patients must have progressed on, be intolerant of, decline, or be ineligible for, all available standard of care therapies with proven benefit.
Part 2 – dose escalation/phase 2a:
Cohort 2: locally advanced or metastatic NSCLC with the presence of a known mutation in KEAP1, NFE2L2 and/or STK11.
- The mutational status of KEAP1, NFE2L2, STK11 and KRAS genes will be performed by locally validated DNA tests. Testing will be performed by sequencing DNA extracted from tissue samples and/or from DNA extracted from blood samples using methods of targeting circulating tumor DNA (ctDNA).
- Patients with known EGFR mutations, BRAF V600E mutations, ALK rearrangements, ROS1 rearrangements, NTRK gene fusions, RET gene fusion and MET exon 14 skipping mutations are excluded; other known mutations identified by a locally validated DNA tests are allowed.
- Patients must have received at least a platinum doublet chemotherapy and an anti-PD-(L)1 antibody unless patients declined or are ineligible for treatment.
- Received no more than 3 lines of systemic anticancer therapy in the recurrent or metastatic setting. Patients with a known KRAS G12C mutation should receive an available, locally approved treatment, which will be considered as one of the 3 prior lines of systemic anticancer therapy, unless patients declined, are intolerant of or are ineligible for treatment.
Cohort 3: Recurrent, unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) (the oropharynx, oral cavity, hypopharynx or larynx).
- Patient must have received platinum containing chemotherapy and an anti-PD-(L)1 antibody in the recurrent or metastatic setting, unless patients declined or are ineligible for treatment
- Received no more than 3 lines of systemic anticancer therapy in the recurrent or metastatic setting
Part 3 and 4 – DRP-104 + Atezolizumab dose escalation/expansion
- Must have prior exposure to therapy with any agent specifically targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1 and/or anti-CTLA-4 antibody)
- Received no more than 3 lines of systemic anticancer therapy in the recurrent or metastatic setting
• Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1.
• Patient must consent to allow the acquisition of existing FFPE tumor tissue, as 17 unstained slides, for performance of correlative studies.
• All SCCHN patients, all NSCLC patients and patients being treated with the combination of DRP-104 and atezolizumab will be required to undergo pre-treatment and post-treatment core or excisional biopsies. These patients will still require an archival tumor sample.
• Adequate baseline organ function as defined in the protocol.
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one highly effe
• Target disease exceptions
o Patients with primary central nervous system tumors and hepatocellular carcinoma.
o Patients with progressive or symptomatic brain metastases. Patients with brain metastases may be included in this trial as long as the brain metastases have completed definitive treatment at least 14 days prior to meeting eligibility and are radiologically stable (i.e., without evidence of progression on screening imaging assessment, [Note: repeat imaging should be performed during study screening]). Patients must be clinically stable and have discontinued anti-seizure medications and steroids, except for physiologic steroid dosing (=10 mg/day of prednisone equivalents), for at least 14 days prior to Cycle 1 Day 1.
o Leptomeningeal disease.
o Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 8 weeks prior to Cycle 1 Day 1 and must have discontinued steroids, except for physiologic steroid dosing (=10 mg/day of prednisone equivalents).
o Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Patients with indwelling catheters (e.g., PleurX) are allowed regardless of drainage frequency.
• Prior therapy
o Patients who have not recovered to grade 1 or baseline from adverse events (CTCAE v 5.0) related to prior therapy excluding alopecia, peripheral neuropathy and ototoxicity, which are excluded if = grade 3. Note: any lymphopenia due to previous therapy must have recovered to grade 1 or baseline prior to enrollment.
o Prior glutaminase inhibitor use (excluded in Part 2: Cohorts 2 and 3 only)
o Prior systemic anticancer treatment (i.e. chemotherapy, biologic therapy [i.e. small molecular inhibitors], monoclonal antibodies, investigational agents]) within 21 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1. If a patient is receiving an anti-PD-1 or anti-PD-L1 antibody on a shorter frequency, ie every two weeks, then the patient is eligible if last dose is 14 days prior to Cycle 1 Day 1. Note: Patients must have recovered from all AEs due to previous therapies to CTCAE v 5.0 grade 1 or baseline, excluding lymphopenia, alopecia, peripheral neuropathy and ototoxicity, which are excluded if >= grade 3.
o Prior small port palliative radiotherapy within 14 days prior to Cycle 1 Day 1 or within 42 days prior to Cycle 1 Day 1 from definitive local control radiation (any dose greater than 50 Gy, within 42 days of Cycle 1 Day1). Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
o Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide, abiraterone, or orteronel within 2 weeks prior to Cycle 1 Day 1. Patients with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Patients with prostate cancer may also remain on low-dose prednisone or prednisolone up to 10 mg/day.
- Patients with hormone positive breast cancer may remain on endocrine therapy.
o Prior therapy with long acting myeloid growth factor or from a short acting myeloid growth factor within 14 days or 7 days prior to Cycle 1 Day 1, respectively
o Any major surgery within 21 days prior to Cycle
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method