Treating Multiple Myeloma and Diffuse Large B Cell Lymphoma by Targeting the NF-κB Pathway with the First-in-Class GADD45β/MKK7 Inhibitor, DTP3

Disease specific inclusion criteria [MM] 1. Documented diagnosis of multiple myeloma (IMWG 2014 criteria) 2. Any R-ISS stage 3. Measurable disease as determined by at least one of: • Serum M-protein ≥ 500 mg/dL • Urine M-protein ≥ 200 mg/24 hour • Involved serum free light chain (sFLC) level ≥10 mg/dL,provided that serum sFLC ratio is abnormal 4. Has previously been treated with an ImiD,a proteasome inhibitor and an anti-CD38 antibody 5. Previous treatment with at least 2 prior regimens 6. Relapsed (after most recent regimen) or refractory disease [refractory defined as either best response of progression on previous regimen or progression within 6 months of achieving PR (or better) on previous regimen] 7. Requires active therapeutic intervention (in the judgement of the investigator) 8. Not currently a candidate for stem cell transplantation or CAR T-cell therapy Disease specific inclusion criteria [DLBCL] 9. Documented diagnosis of DLBCL [WHO 2016 criteria] • Diffuse large B-cell lymphoma – de novo or transformed (from follicular lymphoma only) • High-grade B-cell lymphoma (MYC with BCL2 and/or BCL6); High-grade B-cell lymphoma (NOS) • Primary mediastinal B-cell lymphoma 10. Non-GCB by local IHC [Dose Expansion Only] 11. Measurable disease as determined by: • CT (or MRI) documentation of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis ≥ 1.0 cm AND baseline FDG-PET scans must demonstrate positive lesion compatibility with CT (or MRI) defined anatomical tumour sites. 12. No available standard of care therapeutic regimens in the opinion of the investigator 13. Relapsed (after most recent regimen) or refractory disease [refractory defined as either best response of progression on previous regimen or progression within 6 months of achieving PR (or better) on previous regimen] 14. Requires active therapeutic intervention (in the judgement of the investigator) 15. Not currently a candidate for stem cell transplantation or CAR T-cell therapy General inclusion criteria: 16. Adequate hematologic function: • ANC ≥ 1 x 109/L (no restriction on prior growth factor support) • Platelet count ≥50 x 109/L (no platelet transfusions permitted in 7 last days prior to assessment). Platelet counts of < 50 x 109/L may be considered,on a case by case basis,for patients with significant malignant bone marrow involvement,after discussion with the medical monitor • Hb ≥8 gm/dL (no RBC transfusions permitted in 7 last days prior to assessment) • aPTT and PT within institutional normal range (unless patient is on full-dose warfarin,in which case INR within normal institutional therapeutic range is acceptable) 17. No evidence of bleeding diathesis or coagulopathy 18. Adequate laboratory biochemical function: • Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 30 mL/min (Cockcroft-Gault calculation) • Bilirubin level < 1.5 X ULN. • AST and ALT < 2.5 X ULN 19. ECOG performance status 0-2 20. Age > 16 years 21. Written informed consent prior to admission into the study

1. Primary or secondary CNS lymphoma 2. T-cell rich B-cell lymphoma 3. Plasma cell leukaemia 4. POEMS syndrome (polyneuropathy,organomegaly,endocrinopathy,monoclonal protein,and skin changes) 5. Primary amyloidosis 6. Clinically significant (in the opinion of the investigator) cardiovascular disease,such as: • History of myocardial infarction,acute coronary syndromes (including unstable angina),coronary angioplasty/stenting/bypass grafting within the past 6 months prior to the date of consent • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system • Severe cardiac arrhythmia requiring medication or severe conduction abnormalities • Poorly controlled hypertension (resting diastolic blood pressure > 100 mmHg) • Clinically significant valvular disease,cardiomegaly,ventricular hypertrophy,or cardiomyopathy,QTc prolongation [defined as a QTc interval > 450 msec (males) or > 470 msec (females)] or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate < 50 beats/min) 7. Clinically significant (in the opinion of the investigator) cerebrovascular disorders or vascular dementia 8. Clinically significant (in the opinion of the investigator) intercurrent medical or psychiatric illness,including serious active infection 9. Significant neuropathy (Grade 3,Grade 4,or Grade 2 with pain) 10. Concurrent treatment with other experimental drugs 11. A daily requirement for prednisone at a dose of > 10 mg/day (or steroid equivalent) at time of starting the first dose of study drug. Higher doses are permitted for primary disease symptomatic control during the screening period,after discussion with the medical monitor,but this must have been tapered to a dose of ≤10mg/day by the time treatment with DTP3 starts 12. Sem cell transplant (autologous/allogeneic) or CAR T-cell regimen within 12 weeks of the date of consent 13. Participation in another clinical trial with any investigational drug within 28 days prior to the date of consent 14. Prior (non-experimental) MM or DLBCL therapy within 28 days of the date of consent. Concomitant bisphosphonate therapy is permitted 15. Prior radiotherapy within 28 days of the date of consent. Localised palliative radiation therapy to a single site for symptomatic control is acceptable within this period 16. Anticipated need for concurrent radiotherapy during the study 17. Past or current history of other neoplasms,except for • Curatively treated non-melanoma skin cancer • Adequately treated in situ carcinoma of the cervix • Prostate adenocarcinoma with documented PSA value of < 0.1 ng/mL within six weeks of the date of consent • Other cancer curatively treated and with no evidence of disease for at least 3 years before the date of consent. 18. Known HIV infection 19. Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody,hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result 20. Ability to become pregnant (or already pregnant or lactating). However,those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception: i) oral,injected or implanted hormonal contraception and condom,ii) have an intra-uterine device and condom,iii) vasectomised partner or iv) sexual abstinence during the trial and for 6 months after the last dose of DTP3 are considered eligible. Where age appropriate,female patients must be given advice on potential germ cell donation and cryopreservation 21. Male patients with partners of child-bearing potential [unless they agree to take measures not to father children by using one form of highly effective contraception (condom plus spermicide) during the trial and for 90 days after the last date of DTP3]. Where age appropriate,male patients must be given advice on potential germ cell donation and cryopreservation,Men with pregnant or lactating partners should be advised to use barrier method contraception (for example,condom plus spermicidal gel) to prevent exposure to the foetus or neonate.