A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
Status and phase
Completed
Phase 1
Conditions
Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
Treatments
Biological: CJM112
Biological: PDR001
Biological: ACZ885
Drug: TMT212
Drug: EGF816
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
The purpose of this study was to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.
Full description
This was a Phase Ib, multi-center, open-label study, to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 in combination with canakinumab, CJM112, trametinib and EGF816 and single agent (s.a.) canakinumab in subjects with Triple Negative Breast Cancer (TNBC), Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC). The study comprised a dose escalation part for combination treatments only, followed by a dose expansion part.
Enrollment
283 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
Inclusion criteria
- Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available.
Patients must fit into one of the following groups:
- Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
- Non-small cell lung cancer (NSCLC) (adenocarcinoma)
- Triple Negative Breast Cancer (TNBC) (D
- ECOG Performance Status ≤ 2
- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and again during therapy on this study.
- Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.
- Written informed consent must be obtained prior to any screening procedures other than procedures performed as part of standard of care.
Exclusion criteria
- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
- Impaired cardiac function or clinically significant cardiac disease.
- Patients with active, known or suspected autoimmune disease.
- Human Immunodeficiency Virus infection at screening.
- Escalation part: Active Hepatitis B (HBV) or Hepatitis C (HCV) virus infection at screening.
Expansion part: Patients with active HBV or HCV are excluded, excepting those patients undergoing treatment for HBV or HCV.
- Malignant disease, other than that being treated in this study.
- Recent systemic anti-cancer therapy
- Active infection requiring systemic antibiotic therapy.
- Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency or treatment with low, stable dose of steroid (<10mg/ day prednisone or equivalent) for stable CNS metastatic disease.
- Patients receiving systemic treatment with any immunosuppressive medication, excepting the above
- Use of any live vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
- Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
- Recent use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF)
Additional exclusion criteria for Combination arm PDR001+canakinumab and single-agent canakinumab
- Patients with tuberculosis (TB). Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
- Patients who have been infected with HBV or HCV including those with inactive disease.
Additional exclusion criteria for Combination arm PDR001+CJM112
- Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
- Patients with history of and/or active inflammatory bowel disease.
- Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
- Active candida infection, including mucocutaneous infection or history of invasive candidiasis.
Additional exclusion criteria for Combination arm PDR001+trametinib
- Patients with history of retinal vein oclusion.
- Patients with history of interstitial lung disease or pneumonitis.
- Patients with cardiomyopathy and/or LVEF < LLN.
- Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners.
- Hemoglobin (Hgb) < 9 g/dL without growth factor or transfusion support
- Women of child-bearing potential using hormonal contraception, unless an additional contraception method is also used according to the Mekinist® label.
Additional exclusion criteria for Combination arm PDR001+EGF816
- NSCLC patients with EGFR mutant tumors.
- Strong inhibitors and strong inducers of CYP3A4 should not be used concomitantly.
- Patients with history of interstitial lung disease.
- Patients who have been infected with HBV or HCV including those with inactive disease.
- Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners
- Patients cannot have received radiotherapy to lung fields within 6 months of study treatment start.
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
283 participants in 23 patient groups
PDR + ACZ 100mg Q8W
Experimental group
Description:
PDR + ACZ 100mg Q8W
Treatment:
Biological: ACZ885
Biological: PDR001
PDR + ACZ 300mg Q8W
Experimental group
Description:
PDR + ACZ 300mg Q8W
Treatment:
Biological: ACZ885
Biological: PDR001
PDR + ACZ RDE TNBC
Experimental group
Description:
PDR + ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)
Treatment:
Biological: ACZ885
Biological: PDR001
PDR + ACZ RDE NSCLC
Experimental group
Description:
PDR + ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)
Treatment:
Biological: ACZ885
Biological: PDR001
PDR + ACZ RDE CRC
Experimental group
Description:
PDR + ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)
Treatment:
Biological: ACZ885
Biological: PDR001
PDR + CJM 25mg Q4W
Experimental group
Description:
PDR + CJM 25mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 75mg Q4W
Experimental group
Description:
PDR + CJM 75mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 225mg Q4W
Experimental group
Description:
PDR + CJM 225mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 450mg Q4W
Experimental group
Description:
PDR + CJM 450mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 450mg Q2W
Experimental group
Description:
PDR + CJM 450mg Q2W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 900mg Q4W
Experimental group
Description:
PDR + CJM 900mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 900mg Q2W
Experimental group
Description:
PDR + CJM 900mg Q2W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + CJM 1200mg Q4W
Experimental group
Description:
PDR + CJM 1200mg Q4W
Treatment:
Biological: CJM112
Biological: PDR001
PDR + TMT 0.5mg QD
Experimental group
Description:
PDR + TMT 0.5mg QD
Treatment:
Drug: TMT212
Biological: PDR001
PDR + TMT 1mg QD
Experimental group
Description:
PDR + TMT 1mg QD
Treatment:
Drug: TMT212
Biological: PDR001
PDR + TMT 1mg QD, 3 Weeks on/1 Week off
Experimental group
Description:
PDR + TMT 1mg QD, 3 Weeks on/1 Week off
Treatment:
Drug: TMT212
Biological: PDR001
PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off
Experimental group
Description:
PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off
Treatment:
Drug: TMT212
Biological: PDR001
PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off
Experimental group
Description:
PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off
Treatment:
Drug: TMT212
Biological: PDR001
PDR + EGF816 25mg QD
Experimental group
Description:
PDR + EGF816 25mg QD
Treatment:
Drug: EGF816
PDR + EGF816 50mg QD
Experimental group
Description:
PDR + EGF816 50mg QD
Treatment:
Drug: EGF816
s.a. ACZ RDE TNBC
Experimental group
Description:
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)
Treatment:
Biological: ACZ885
s.a. ACZ RDE NSCLC
Experimental group
Description:
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)
Treatment:
Biological: ACZ885
s.a. ACZ RDE CRC
Experimental group
Description:
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)
Treatment:
Biological: ACZ885
Trial contacts and locations
23
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Data sourced from clinicaltrials.gov
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