Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab with or without Acalabrutinib in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab

This is a Phase 1/2a, multicenter, dose escalation, consecutive-cohort, open-label trial of BI-1206 in combination with rituximab with or without acalabrutinib in subjects with indolent relapsed or refractory B-cell NHL, sub-types FL (except FL grade 3B), MZL, and MCL.

Phase 2a, consists of signal seeking cohorts followed by a randomized, parallel, two-arm dose optimization.

The trial consists of 2 main parts:

Phase 1

- Dose Escalation, with two different Arms assessing IV or SC dosing of BI-1206 in combination with rituximab, with dose escalation cohorts and selection of the IV and SC doses of BI-1206 for Phase 2a

Phase 2a

• Dose Expansion, with one expansion cohort evaluating the selected IV dose of BI-1206 in combination with rituximab
• Signal Seeking, assessing IV and SC dosing of BI-1206 in combination with rituximab and acalabrutinib. The Signal Seeking will consist of a Safety Run-in and an Expansion
• Dose Optimization to select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib

Inclusion Criteria:

1. Are ≥ 18 years of age by initiation of study treatment.
2. Have B-cell NHL proven by histology, with histological subtypes limited to follicular lymphoma (FL) (except FL grade 3B), MCL and marginal zone lymphoma (MZL)
3. Have measurable nodal disease
4. Are willing to undergo lymph node biopsies or biopsies of other involved tissue
5. Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists
6. Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen
7. Have a life expectancy of at least 12 weeks
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
9. Have CD20+ malignancy
10. Have hematological and biochemical indices within prespecified ranges

Exclusion Criteria:

1. Have had an allogenic bone marrow or stem cell transplant within 12 months

2. Have presence of active chronic graft versus host disease

3. Have current leptomeningeal lymphoma or compromise of the central nervous system

4. Have transformed lymphoma from a pre-existing indolent lymphoma

5. Have Waldenstrom's Macroglobulinemia or FL grade 3B,

6. Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.

7. Have known or suspected hypersensitivity to rituximab or BI-1206

8. Have cardiac or renal amyloid light-chain amyloidosis

9. Have received any of the following:

   1. Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
   2. Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
   3. Immunotherapy within 8 weeks
   4. Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib

10. Have ongoing toxic manifestations of previous treatments.

11. Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).

12. Have had major surgery from which the subject has not yet recovered.

13. Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.

14. Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).

15. Have an active, known or suspected autoimmune disease.

16. Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])

17. Have current malignancies of other types

All information concerning the product as well as any matter concerning the operation of the Sponsor, such as clinical indications for the drug, its formula, methods of manufacture and other scientific data relating to it, that have been provided by the Sponsor and are unpublished, are confidential and must remain the sole property of the Sponsor. The Investigator will agree to use the information only for the purposes of carrying out this study and for no other purpose unless prior written permission from the Sponsor is obtained.

Within one year from end of study

Paper copy of CSR