Study to Investigate DRP-104 in Adults With Advanced Solid Tumors

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 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 (patients that require transfusion or growth factors need to demonstrate stable hemoglobin of ≥ 9 g/dL over at least a 7-day period after the last transfusion/growth factor injection prior to screening labs to meet eligibility) ; 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 or leptomeningeal disease
* 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.
* Lymphopenia ≤ grade 3 is allowed if not related to prior anticancer therapy. If related to prior anticancer therapy, lymphopenia must resolve to ≤ grade 1 or baseline.
* 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
* Patients must have recovered from all AEs due to previous therapies to CTCAE v 5.0 grade 1 or baseline, excluding, alopecia, peripheral neuropathy and ototoxicity, which must be at least grade 2 or baseline
* 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, 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
* History of organ transplantation and/or hematopoietic stem cell transplantation
* Evidence or history of active or latent tuberculosis infection
* Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1