First-in-human Study of DRP-104 as Single Agent and in Combination With Atezolizumab in Patients With Advanced Solid Tumors.

ID#: NCT04471415

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: August 31, 2020

End Date: July 01, 2023

Contact Information:
Margaret Dugan, MD
973-489-7163
Francois Lafleur, MPH
917-330-3971
Summary:

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of DRP-104 administered via intravenous infusion as a single agent and in combination with atezolizumab in patients with advanced solid tumors and to assess preliminary safety and efficacy in two expansions of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations and advanced squamous cell carcinoma of the head and neck (SCCHN).

Eligibility:



Inclusion Criteria:

- Diagnosis of advanced or recurrent, histologically or cytologically confirmed, measurable by RECIST 1.1 metastatic or unresectable solid tumor

- Patient must have progressed on, be intolerant of, decline, or be ineligible for, all available standard of care therapies

- Part 2: locally advanced or metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation ; Patients must have received at least a platinum doublet chemotherapy and an anti-PD-(L)1 antibody; Received up to 3 lines of systemic anticancer therapy in the recurrent or metastatic setting

- Part 2: Recurrent, unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) (oropharynx, oral cavity, hypopharynx or larynx); Patient must have received platinum containing chemotherapy and antiPD-(L)1 antibody in recurrent or metastatic setting

- Part 3 and 4

- DRP-104 + atezolizumab Prior exposure to any checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PDL2, and/or anti-CTLA-4 antibody)

- ECOG performance 0 or 1

- Patient must consent to allow acquisition of existing FFPE tumor tissue; If unavailable, patient must consent to new pre-treatment tumor biopsy

- All SCCHN patient, all NSCLC patients and all patients treated with combination of DRP-104 and atezolizumab will be required to undergo pre-treatment and post-treatment core or excisional biopsies.

- Pre-treatment and post-treatment core or excisional biopsies are optional for all remaining patients

- Adequate baseline organ function as defined by: Absolute neutrophil count ≥ 1.5 × 109/L (1500/µL); Hemoglobin ≥ 9 g/dL ;Platelets ≥ 75 × 109/L (75,000/µL); Hepatic Total bilirubin ≤1.5 × upper limit of normal (ULN): PT/INR and PTT ≤1.5 × ULN, unless treated with warfarin; AST(SGOT)/ALT(SGPT) ≤3 × ULN or ≤ 5 × ULN for patients with liver metastases; Creatinine clearance ≥ 60 ml/min/1.73m2 measured or calculated

- Cardiac QTc (Fridericia) <470 ms

- Women of child-bearing potential and men who are sexually active must agree to use one highly effective method of contraception

Exclusion Criteria:

- Patients with primary central nervous system tumors and hepatocellular carcinoma

- Patients with progressive or symptomatic brain metastases

- Leptomeningeal disease

- Spinal cord compression not definitively treated with surgery and/or radiation

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage

- Prior glutaminase inhibitor use

- Prior systemic anticancer treatment (i.e. chemotherapy, biologic therapy, monoclonal antibodies, investigational agents) within 21 days or 5 half-lives, whichever is shorter

- Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks prior to enrollment

- Prior small port palliative radiotherapy within 14 days of start of Cycle 1

- Any major surgery within 21 days from start of Cycle 1

- Secondary malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy

- Has a known history of HIV, or HBV

- Gastrointestinal (GI) function impairment or GI disease

- Significant, uncontrolled heart disease and/or cardiac repolarization abnormality

- Exclusion specific to only Part 3 and 4 (DRP-104 combined with atezolizumab): History of severe allergic, anaphylactic to chimeric or humanized antibodies or fusion proteins; Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells; Prior anti-PD-1, anti-PD-L1 and/or anti CTLA4- agent, patient must not have had a serious (> Grade 3) immune-related AE requiring treatment; History of autoimmune disease except hypothyroidism on thyroid replacement hormone therapy; History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis; Patients with underlying condition requiring systemic corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications or other systemic immunosuppressant medications may be enrolled in the study after approval by the Medical Monitor; Evidence or history of active or latent tuberculosis infection; Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1