AN OPEN-LABEL, MULTICENTER, DOSE ESCALATION PHASE IB STUDY WITH EXPANSION COHORTS TO EVALUATE THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS AND THERAPEUTIC ACTIVITY OF RO7009789 (CD40 AGONISTIC MONOCLONAL ANTIBODY) OR BEVACIZUMAB (ANTI-VEGF MONOCLONAL ANTIBODY, PART II) IN COMBINATION WITH VANUCIZUMAB (ANTI-ANG2 AND ANTI-VEGF BI-SPECIFIC MONOCLONAL ANTIBODY) IN PATIENTS WITH METASTATIC SOLID TUMORS

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

* Part I: Advanced/metastatic histologically confirmed solid tumor (except prostate cancer and squamous NSCLC) not amenable to standard therapy
* Part II: Histologically confirmed diagnosis of advanced/metastatic aPROC, HNSCC and non-squamous NSCLC previously treated with anti-PD-L1 inhibitor alone or in combination
* Age * 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy * 16 weeks
* Adequate hematologic and organ function
* Adequate cardiovascular function
* Measurable disease Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria

* Patients with prostate cancer or squamous NSCLC
* Patients who have received prior systemic anti-cancer treatment within the following time frames (see protocol for details)
* Treatment with compounds targeting VEGF or VEGF-R within 12 months prior to enrolment (Part II only)
* Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1
* Chronic daily treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
However, occasional use for the symptomatic relief of medical conditions (e.g.
headache) is allowed
* Patients who have undergone major surgery within 4 weeks prior to study drug administration
* Patients who have undurgone any abdominal surgery or interventions (including colonoscopy)or
significant abdominal traumatic injury within 60 days prior to Day 1 of
Cycle 1
* Known clinically significant liver disease (with the exception of Gilbert's syndrome)
* History of peripheral venous thrombosis or thromboembolic event (within 12 months prior to Cycle 1 Day 1)
* History of hemoptysis (bronchopulmonary hemorrhage) NCI CTCAE * Grade 2 within 4 weeks prior to study drug administration;
* Metastatic disease that involves major airways or blood vessels, or centrally
located mediastinal tumor masses (< 30 mm from the carina) of large volume
* Significant cardio- or cerebrovascular disease within 6 months prior to Cycle 1 Day 1
* History of intra-abdominal inflammatory process within 6 months prior to
Day 1 Cycle 1, including but not limited to: diverticulitis, peptic ulcer disease,
colitis
* History of bowel obstruction and/or clinical signs or symptoms of
gastrointestinal obstruction including sub-occlusive disease, related to the
underlying disease or a requirement for routine parenteral hydration, parenteral
nutrition, or tube feeding. Patients with signs/symptoms of sub-/occlusive
syndrome/bowel obstruction at time of initial diagnosis may be enrolled if
they had received definitive (surgical) treatment for symptom resolution.
* Evidence of abdominal free air not explained by paracentesis or recent
surgical procedure
* Patients with colonic prosthesis (stent) implant in place (as applicable)
* Severe non-healing wound, active ulcer or untreated bone fracture
* Known primary CNS malignancy or symptomatic or untreated CNS metastases.
* Pregnancy, lactation, or breastfeeding
* History of autoimmune diseases
* Patient with HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection
* Severe infections within 4 weeks prior to Cycle 1 Day 1