Treatment of solid tumors, including advanced/unresectable or metastatic cancer and neoadjuvant/resectable MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: CX-072
Product Code: CX-072
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CX-072
Current Sponsor code: CX-072
Other descriptive name: CX-072
Concentrati
Sponsors
CytomX Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age 2. Measurable disease as defined by RECIST v1.1 3. Eastern Cooperative Oncology Group (ECOG) performance status of =1 4. Agree to provide tumor tissue and blood samples for biomarker assessment • Part A: Must agree to provide mandatory archival tumor tissue (formalin-fixed paraffin embedded tumor block or unstained slides) or undergo a new tumor biopsy • Part B: Must agree to provide tumor tissue from the initial diagnostic biopsy and prospectively agree to provide tumor tissue obtained from surgery on study for pathologic analysis and for biomarker assessment 5. Subjects with treated brain metastases are eligible if the brain metastases are stable (no magnetic resonance imaging [MRI] evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study treatment) and the subject does not require radiation therapy or steroids. Active screening for brain metastases (eg, brain computed tomography [CT] or MRI) is not required 6. Screening laboratory values must meet all of the following criteria: • White blood cells >2000/µL or 2.0 × 10 to the power of 9/L • Neutrophils =1500/µL or 1.5 × 10 to the power of 9/L • Platelets =100 × 10 to the power of 3/µL or 100 × 10 to the power of 9/L • Hemoglobin =9.0 g/dL (may have been transfused) or 90.0 g/L • Creatinine =2 mg/dL or 176.8 µmol/L OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) >50 mL/min • AST and ALT =2.5 × upper limit of normal (ULN) • Total bilirubin within ULN (unless diagnosed with Gilbert’s syndrome, those subjects must have a total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. Treatment with cytotoxic chemotherapy, biologic agents, radiation, immunotherapy, or any investigational agent within 28 days prior to the first dose of study treatment. This interval can be reduced to 2 weeks for subjects who received bone-only radiation therapy or for subjects whose most recent prior therapy was a single-agent, small-molecule kinase inhibitor having a half-life of 3 days or less. - For Cohort A2: Prior anti-PD-1/PD-L1 antibody given as a single agent is not excluded within the 28 days prior to the first dose of study treatment. Time from last dose of prior anti-PD-1/PD-L1 inhibitor to first dose of study treatment must be at least the same length as the time interval of the prior PD-1/PD-L1 dosing schedule (eg, if prior PD-1/PD-L1 dosing was once every 14 days, then the last dose must have been at least 14 days prior to first dose of study treatment) 2. Prior therapy with a chimeric antigen receptor T cell–containing regimen 3. History of active autoimmune disease(s) including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies, type 1 insulin-dependent diabetes mellitus 4. History of myocarditis regardless of the cause 5. History of intolerance to prior checkpoint inhibitor therapy defined as the need to discontinue treatment due to an irAE 6. History of toxic epidermal necrolysis or Stevens-Johnson syndrome 7. History of any syndrome or medical condition that required treatment with systemic steroids (=10 mg daily prednisone equivalents) or immunosuppressive medications. However, subjects who required brief courses of steroids (eg, as prophylaxis for IV contrastor for treatment of an allergic reaction) may be eligible with Sponsor approval. Inhaled or topical steroids are permitted. 8. Baseline corrected QT interval (QTc) >470 ms. If a subject starts on a QTc prolonging drug(s), a series of electrocardiograms (ECGs) should be obtained to redefine the baseline QTc. 9. Unresolved acute toxicity CTCAE v5.0 Grade =1 (or baseline, whichever is greater) from prior anticancer therapy. Alopecia and other nonacute toxicities are acceptable. 10. History of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity to any Probody therapeutic 11. Subjects with known human immunodeficiency virus, acquired immune deficiency syndrome, or any related illness 12. Subjects with acute or chronic hepatitis B or C 13. History of allogeneic tissue/solid organ transplant, stem cell transplant, or bone marrow transplant 14. Major surgery (eg, that required general anesthesia) within 4 weeks prior to the first dose of study treatment (and must be confirmed to be completely healed), or minor surgery (eg, not involving chest, abdomen, or intracranial structures) or gamma knife treatment (with adequate healing) within 14 days prior to first dose of study treatment (excluding biopsies conducted with local/topical anesthesia) if complete healing is confirmed 15. History of active malignancy not related to the cancer being treated within the previous 2 years, with the exception of localized cancers that are considered cured and, in the opinion of the Investigator, present a low risk for recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ of the pros
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: • To obtain evidence of antitumor effect of CX-072 in combination with ipilimumab in subjects with solid tumors based on the objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Part B: • To obtain evidence of antitumor effect of CX-072 in combination with ipilimumab in subjects with solid tumors based on pathologic response following neoadjuvant administration of combination treatment;Secondary Objective: Part A: • Safety and tolerability of CX-072 in combination with ipilimumab in subjects with solid tumors • Evaluate antitumor activity in subjects with solid tumors treated with CX-072 in combination with ipilimumab • Characterize the pharmacokinetics (PK) of CX-072 and ipilimumab • Characterize the incidence of CX-072 antidrug antibodies (ADAs) and ipilimumab ADAs Part B: • Safety and tolerability of CX-072 in combination with ipilimumab in subjects with solid tumors • Evaluate antitumor activity in subjects with solid tumors treated with CX-072 in combination with ipilimumab • Characterize the PK profile of CX-072 and ipilimumab • Characterize the incidence of CX-072 ADAs and ipilimumab ADAs;Primary end point(s): - Objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as defined in the Common Core Protocol (Appendix A) - Pathologic response following neoadjuvant administration of combination treatment;Timepoint(s) of evaluation of this end point: PART A: Radiographic Tumor Assessment and Tumor Response Evaluation : At screening and Scan q8w (±1w) for 12 months and q12w (±1w) thereafter until confirmed progression as assessed by irRECIST PART B: Pathologic Response Assessment: Study day 43 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PART A: - Adverse Event Assessment - Objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 - Duration of response (DOR) - Time to response (TTR) - Progression-free survival (PFS) - Overall survival (OS) - PK - CX-072 antidrug antibodies (ADAs) and ipilimumab ADAs PART B: - Adverse Event Assessment - Objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 prior to surgery - Relapse-free survival (RFS) - PK - CX-072 antidrug antibodies (ADAs) and ipilimumab ADAs;Timepoint(s) of evaluation of this end point: PART A: - Radiographic Tumor Assessment and Tumor Response Evaluation : At screening and Scan q8w (±1w) for 12 months and q12w (±1w) thereafter until confirmed progression as assessed by irRECIST - CX-072 ADAs: Study day 1, 22, 64, 85, 127, then q42d, Last Tx Day +30d (-2/+7d), Last Tx Day +90d then q90d (±14d) - Ipilimumab ADAs: Study day 1, 64 PART B: - Radiographic Tumor Assessment and Tumor Response Evaluation : At screening, study day 40, Scan q12w (±1w) until relapse - CX-072 ADAs: Study day 1, 22, 85, 106, 127, 155, 183, then q14d, Last Tx Day +30d (-2/+7d), Last Tx Day +90d then q90d (±14d) - Ipilimumab ADAs: Study day 1, 106 PART A & B: - Adverse Event Assessment per Protocol - Collect PK samples as shown in Table 3 of Protocol | — |
Countries
Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Team
CytomX Therapeutics, Inc.
Outcome results
None listed