Adult HLA-A*02-positive patients who have been diagnosed with unresectable, locally advanced and/or metastatic colorectal cancer before first-line chemotherapy. Patients must have completed a 12 week first-line oxaliplatin-based standard chemotherapy (e.g. FOLFOX or XELOX) with either complete or partial response or stable disease as the outcome.
Conditions
Interventions
Product Name: IMA910
Product Code: IMA910
Pharmaceutical Form: Powder for suspension for injection
Trade Name: Endoxana
Product Name: Endoxana (Cyclophosphamide)
Pharmaceutical Form: Powder for solut
Sponsors
immatics biotechnologies GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Aged at least 18 years • HLA type: HLA-A*02-positive • Histologically confirmed colorectal adenocarcinoma (CRC) • Radiological evidence (CT/MRI) of unresectable locally advanced and/or metastatic CRC prior to 12 week first-line oxaliplatin-based standard chemotherapy • 12 week first-line chemotherapy with an oxaliplatin-based regimen according to an established standard protocol (e.g. FOLFOX or XELOX) administered at the following minimum dosages over this 12 week period: Oxaliplatin 400 mg/m2, Fluorouracil (5FU) 10.000 mg/m2 or Capecitabine 84.000 mg/m2 (a time window for application of first-line chemotherapy of +4 weeks is allowed) • Response (CR, PR) or stabilization (SD) following a 12 week first-line oxaliplatin-based standard chemotherapy shown by radiological evidence (CT/MRI after last cycle of first-line oxaliplatin-based standard chemotherapy compared to CT/MRI taken before start of first-line oxaliplatin-based standard chemotherapy) • Patients accept a chemotherapy-free interval under close observation (CT or MRI scans performed every 9 weeks) • Maximum period between start of study treatment and start of the last cycle of standard chemotherapy (= first day of last cycle of standard chemotherapy) is 42 days; minimum period is 18 days • Currently no other standard therapy indicated • Karnofsky Performance Status ?80% • Able to understand the nature of the study and give written informed consent • Willing and ability to comply with the study protocol for the duration of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Any adjuvant systemic or local chemotherapy if ended ?6 months before start of systemic first-line oxaliplatin-based standard chemotherapy • Progressive disease during or at the end of 12 week systemic first-line oxaliplatin based standard chemotherapy • CT/MRI scans taken more than 9 weeks before start of first-line oxaliplatin-based standard chemotherapy • Response to 12 week first-line oxaliplatin-based standard chemotherapy resulting in resectable disease; curative treatment intended • Immunosuppressive therapy within 10 days before first vaccination e.g. corticosteroid treatment (inhalative corticosteroids for e.g. asthma are allowed) • Radiotherapy during and/or following the 12 week first-line oxaliplatin-based standard chemotherapy (palliative radiotherapy for bone metastasis is allowed) • Concurrent or prior participation in a clinical trial applying interventional procedures (e.g. application of investigational drugs, surgical interventions) within the last 30 days • History of other malignant tumours within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ • Presence of known brain metastasis on MRI or CT scans • Current partial or complete bowel obstruction • Patients with a history or evidence of systemic autoimmune disease • Any vaccination within 2 weeks before first vaccination • Any planned prophylactic vaccination from study entry until the end of the induction period (Week 6 after first vaccination, exception: if medically indicated) • Major surgery =4 weeks before first vaccination • Any of the following abnormal laboratory values: ? Haematology: ? Hb 1.5 x upper normal limit (unless a history of Gilbert’s disease) ? ALAT or ASAT >3 x upper normal limit (>5 x ULN if liver metastases are present) ? Alkaline Phosphatase >3 x upper normal limit (>5 x ULN if liver metastases are present) ? Renal function: serum creatinine >200 µmol/L (2.3 mg/dL) • Known active hepatitis B or C infection • Known HIV infection • Active infections requiring oral or intravenous antibiotics • Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues. Examples are: rabies, Mycobacterium tuberculosis, Coccidioides immitis • Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, including gastrointestinal, hepatic, renal, respiratory, cardiovascular, haematological, coagulation, metabolic or hormonal diseases with clinically relevant abnormal organ function for example: ? Heart failure or non-compensated active heart disease (=NYHA Class III and IV) ? Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension ? Symptomatic neurotoxicity (motor or sensory) = Grade 3 according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) ? Severe pulmonary dysfunction • Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator’s opinion • Pregnancy or breast-feeding • Hypersensitivity to the study drugs (cyclophosphamide, GM-CSF, IMA910) including excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the present phase 1/2 study are to determine whether IMA910 as single agent with GM-CSF as adjuvant following pre-treatment with low-dose cyclophosphamide is safe and shows sufficient anti-tumor effectiveness in patients with advanced CRC to warrant further development. ;Secondary Objective: Secondary objectives of this study are investigation of immunological parameters and additional effectiveness endpoints. Furthermore, a sufficient enhancement of immune response, safety and effectiveness of IMA910 as single agent with GMCSF in combination with imiquimod following pre-treatment with low-dose cyclophosphamide will be investigated in a 2nd cohort of patients.;Primary end point(s): • Safety • Disease control rate (DCR = CR + PR + SD) at Visit 14 (= 27 weeks of vaccination) according to RECIST The primary safety endpoint of this study is evaluated with particular focus on the safety data of the first 6 patients who are enrolled according to an enrolment plan. The primary effectiveness endpoint of this study is defined as the DCR at Visit 14 (=27 weeks of vaccination). This endpoint represents a composite of the objective response rate (ORR) and stable disease (SD) rate, where ORR is defined as the complete response (CR) rate plus partial response (PR) rate. All deaths regardless of cause will be considered as events for the assessment of DCR. The assessment of the primary effectiveness endpoint will be based on RECIST. | — |
Countries
Bulgaria, Germany, Hungary, Latvia, United Kingdom
Outcome results
None listed