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Official Title

A Phase 1b Open-Label Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

Phase
Phase 1
Sponsor
ADC Therapeutics S.A.
Enrollment
200
Timeline
Jun 2022 → Oct 2027
About This Study

The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab, and to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combinations.

Eligibility Criteria

Inclusion Criteria

  • 1Male or female participant aged 18 years or older
  • 2Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in Part 1; and at least one systemic treatment regimen in Part 2
  • 3LBCL:
  • 4Part 2 Arm E enrollment focused on LBCL only
  • 5DLBCL, not otherwise specified (NOS)
  • 6Germinal Center B-cell type
  • 7Activated B-cell type
  • 8Transformed FL (note: patients with transformed FL must have received at least one line of systemic therapy post-transformation to be eligible)
  • 9HGBCL, with MYC and BCL2 and/or BCL6 rearrangements
  • 10HGBCL, NOS
  • 11FL Grade 3b
  • 12Arm F and Part 1 Arm E:
  • 13All LBCL histologies listed above
  • 14FL (Grade 1-3a)
  • 15MZL
  • 16For Arm C only:
  • 17All histologies listed above
  • 18DLBCL (including transformed diseases)
  • 19MCL
  • 20BL
  • 21Life expectancy of at least 24 weeks according to Investigator's judgement
  • 22Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
  • 23Measurable disease as defined by the 2014 Lugano Classification
  • 24Availability of formalin-fixed paraffin-embedded tumor tissue block
  • 25ECOG performance status 0 to 2
  • 26Adequate organ function
  • 27Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. Arm E: WOCBP must agree to use contraceptive methods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 18 months after pretreatment with obinutuzumab. Arm F: WOCBP must agree to use contraceptive methods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable)
  • 28Patients 80 years of age and older at the time of signing the informed consent must be deemed fit by Cumulative Illness Rating Scale - Geriatric (CIRS-G scale), defined as no score of 3-4 in any category AND \< 5 categories with a score of 2 excluding hematologic criteria

Exclusion Criteria

  • 1Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human ADA to a CD19 antibody
  • 2Previous therapy with loncastuximab tesirine
  • 3Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied to relevant arm and/or cohort of the specific drug administered)
  • 4Participants who received previous treatment of polatuzumab vedotin containing regimen will be excluded from Arm C
  • 5Participants who received previous treatment of glofitamab containing regimen will be excluded from Arm E
  • 6Participants who received previous treatment of mosunetuzumab containing regimen will be excluded from Arm F
  • 7Human immunodeficiency virus (HIV) seropositive
  • 8Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
  • 9Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
  • 10History of confirmed progressive multifocal leukoencephalopathy
  • 11History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
  • 12Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
  • 13Breastfeeding or pregnant
  • 14Significant medical comorbidities
  • 15Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), unless approved by the Sponsor
  • 16Live vaccine within 4 weeks prior to C1D1
  • 17Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from acute non-hematologic toxicity (excluding alopecia) due to previous therapy prior to screening
  • 18Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary
  • 19Prior allogeneic stem cell transplant and solid organ transplant
  • 20Autologous stem cell transplant within 100 days prior to C1D1
  • 21History of central nervous system (CNS) lymphoma or leptomeningeal infiltration
  • 22Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • 23Known active infection, reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within four weeks prior to C1D1
  • 24Active or history of autoimmune disease or immune deficiency, motor neuropathy considered of autoimmune origin and other CNS autoimmune diseases, including but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with, with certain exceptions
  • 25Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, cluster of differentiation 137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines and monoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of need for systemic immunosuppressive medication during study treatment, with certain exceptions
  • 26Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primary refractory patients (progressive or persistent disease within 30 days) to CAR-T-cell therapy are not eligible
  • 27Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo
  • 28Any history of immune-related Grade ≥3 AE with the exception of endocrinopathy managed with replacement therapy
  • 29Ongoing corticosteroid use greater than 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment
  • 30Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
  • 31Arm E only: Known history of hypersensitivity to obinutuzumab

Locations

42 sites participating in this study

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

Recruiting

University of California San Francisco - Fresno Center for Medical Education and Research

Clovis, California 93611

Recruiting

Scripps Health - Prebys Cancer Center

San Diego, California 92103

Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →