Professor Chan Cheah

Janssen Research & Development, LLC

Phase I

• Diffuse Large B-Cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Marginal Zone Lymphoma
• Waldenstrom’s Macroglobulinaemia
• Mantle Cell Lymphoma
• Small Lymphocytic Leukaemia
• Chronic Lymphocytic Leukaemia

This trial is suitable for patients with b-cell lymphoma or chronic lymphocytic leukaemia that has returned, worsened or not responded to previous treatment. Patients will receive JNJ-75348780, which is a bispecific antibody that works by stimulating the immune system to destroy cancer cells. JNJ-75348780 will be administered once weekly through an injection under the skin until it no longer works or side effects are unacceptable.

Inclusion Criteria:

1. ≥18 years of age
2. Histologic documentation of disease: B-cell NHL or CLL requiring therapy.
   1. B-cell NHL: All participants must have relapsed or refractory disease. In addition, the following disease-specific criteria outlined below must be met.
      • If DLBCL: Received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent.
      • If FL/MZL (except MALT), or WM: Previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody.
      • If MCL: Previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody.
   2. CLL or SLL: Relapsed or refractory with at least 1 prior line of systemic therapy containing a BTK inhibitor.
3. Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1
4. Hematology laboratory parameters must meet the protocol criteria
5. Clinical chemistry laboratory parameters must be within protocol ranges
6. Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia’s formula [QTcF]) ≤480 milliseconds based on the average of triplicate assessments performed no more than 5 (±3) minutes apart
7. Women of childbearing potential must have a negative highly sensitive serum (b-human chorionic gonadotropin) at screening and prior to the first dose of study drug.
8. Women must be:
   1. Not of childbearing potential
   2. Of childbearing potential and practicing a highly effective, preferably user independent method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 90 days after last dose
9. Men must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak.
10. Women must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 90 days after the last study drug administration.

Exclusion Criteria:

• Known active CNS involvement with lymphoma.
• Prior solid-organ transplantation.
• Either of the following:
  • Received an autologous stem cell transplant ≤3 months before the first dose of JNJ-75348780.
  • Prior treatment with allogenic stem cell transplant ≤6 months before the first dose of JNJ-75348780, has evidence of graft versus host disease, or requires immunosuppressant therapy.
• Prior chemotherapy, targeted therapy, immunotherapy, radiotherapy (with the exclusion of palliative radiation to limited sites that do not interfere with response assessment based on a sufficient number of other sites), or treatment with an investigational anticancer agent or an investigational drug (including investigational vaccines) within 2 weeks before the first administration of study drug. For investigational agents where the half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives.
• Active autoimmune disease that requires systemic immunosuppressive medications (example, chronic corticosteroid, methotrexate, or tacrolimus).

Alex Zagwocki

azagwocki@linear.org.au

6382 5127

75348780LYM1001

NCT04540796