Lispro-PH20 (insulin lispro/rHuPH20) / Halozyme - LARVOL DELTA

[VIRTUAL] Phase III Study of Daratumumab/rhuph20 (nsc- 810307) + Lenalidomide or Lenalidomide As Post-Autologous Stem Cell Transplant Maintenance Therapyin Patients with Multiple Myeloma (mm) Using Minimal Residual Disease Todirect Therapy Duration (DRAMMATIC study): SWOG s1803 (ASH 2020) - "A total of 1100 pts will be accrued to initial step 1 to allow for a 5% drop out and allow 950 pts for the second randomization. As of Aug 1, 171 pts are enrolled for screening among whom 133 have been randomized."

Clinical • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial (clinicaltrials.gov) - P3; N=1450; Recruiting; Sponsor: ECOG-ACRIN Cancer Research Group; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

[VIRTUAL] FACILITATED IMMUNOGLOBULIN ADMINISTRATION REGISTRY AND OUTCOMES STUDY (FIGARO): INTERIM RESULTS IN PATIENTS WITH SECONDARY IMMUNODEFICIENCY DISEASES (SID) (EHA 2020) - P=N/A, P3 | "Facilitated subcutaneous immunoglobulin (fSCIG) is a dual-vial unit of recombinant human hyaluronidase (rHuPH20) and 10% normal immunoglobulin G (IgG) solution...The indications for IgG treatment were CLL (n=12), indolent lymphoma (n=2), B-cell non-Hodgkin’s lymphoma (n=1), diffuse large B-cell lymphoma (n=1), Hodgkin’s disease (n=1), Hodgkin’s lymphoma after autologous transplantation (n=1), rituximab therapy (n=1), and immunosuppressive therapy for rheumatism (n=1)...Study recruitment and patient observation continue. Baxalta (a Takeda company) funded this study and writing support."

Clinical • Chronic Lymphocytic Leukemia • Dermatology • Dermatopathology • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Immunodeficiency • Transplantation

SUBCUTANEOUS DARATUMUMAB (DARA SC) + CYCLOPHOSPHAMIDE, BORTEZOMIB, AND DEXAMETHASONE (CYBORD) IN PATIENTS WITH NEWLY DIAGNOSED AMYLOID LIGHT CHAIN (AL) AMYLOIDOSIS: SAFETY RUN-IN RESULTS OF ANDROMEDA (EHA 2018) - P3; "In the safety run-in, patients received a concentrated co-formulation of DARA (1,800 mg in 15 mL) and recombinant human hyaluronidase enzyme (rHuPH20; 30,000 U) in a single, pre-mixed vial, given by manual SC injection qw in Cycles 1-2, q2w in Cycles 3-6, and q4w thereafter 2 y. Cyclophosphamide 300 mg/m2 PO or IV and bortezomib 1.3 mg/m2 SC were given on Days 1, 8, 15, 22 of each 28-day cycle for 6 cycles and dexamethasone 40 mg was given qw. DARA-CyBorD is tolerable in patients with AL amyloidosis, with a low IRR rate and no new safety signals. The limited incidence of dyspnea and peripheral edema indicate a low risk for volume overload."

Clinical • Hematological Malignancies

Hyaluronidase-Assisted Immunoglobulin Delivery: Initial Results from the Register Study FIGARO (DGHO 2019) - "Introduction: fSCIG (HyQvia) is a dual-vial unit consisting of recombinant human hyaluronidase (rHuPH20) and 10% normal immunoglobulin (IgG) solution. fSCIG infusions offer the flexibility to be performed by the patient at home or in the hospital setting. Dosing schedule allows variability, but the majority of infusions are administered every 4 weeks into one infusion site. The cohort is recruiting and patient observation continues."

[VIRTUAL] Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2020) - P3 | "In the phase 1b study of DARA plus the IMiD pomalidomide, D-Pd induced deep responses and was well tolerated in pts with heavily pretreated RRMM, including those with prior lenalidomide (len) treatment...Prior to protocol amendment, pts received DARA IV 16 mg/kg (n=7); after protocol amendment, all pts received DARA SC 1,800 mg co-formulated with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.)...The IRR rate was very low and administration duration short, thus increasing convenience for pts and decreasing treatment burden. Collectively, these data show that D-Pd is an effective and convenient treatment for pts with RRMM who received ≥1 prior therapy, including len and a PI."

Clinical • P3 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • CD38

[VIRTUAL] Interim Results of a Time and Motion Survey Regarding Subcutaneous Versus Intravenous Administration of Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2020) - P3 | "To reduce this burden, DARA subcutaneous (SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 [rHuPH20; 2000 U/ml; ENHANZE® drug delivery technology, Halozyme, Inc., San Diego, CA, USA]) was developed. Conclusions : Results of this time and motion survey indicate that DARA SC is associated with less active HCP time spent on drug preparation and drug administration/patient care compared with DARA IV. This reduced treatment burden may translate into advantages for patients (less time away from home, family, and/or work) and efficiencies for HCPs and healthcare facilities (ability to treat a greater number of patients)."

Clinical • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease • Oncology

[VIRTUAL] Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2020) - P3 | "In the phase 1b study of DARA plus the IMiD pomalidomide, D-Pd induced deep responses and was well tolerated in pts with heavily pretreated RRMM, including those with prior lenalidomide (len) treatment...Prior to protocol amendment, pts received DARA IV 16 mg/kg (n=7); after protocol amendment, all pts received DARA SC 1,800 mg co-formulated with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.)...The IRR rate was very low and administration duration short, thus increasing convenience for pts and decreasing treatment burden. Collectively, these data show that D-Pd is an effective and convenient treatment for pts with RRMM who received ≥1 prior therapy, including len and a PI."

Clinical • P3 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • CD38

[VIRTUAL] Subcutaneous Daratumumab (DARA SC) Plus Standard-of-Care (SoC) Regimens in Multiple Myeloma (MM) across Lines of Therapy in the Phase 2 Pleiades Study: Initial Results of the Dara SC Plus Carfilzomib/Dexamethasone (D-Kd) Cohort, and Updated Results for the Dara SC Plus Bortezomib/Melphalan/Prednisone (D-VMP) and Dara SC Plus Lenalidomide/Dexamethasone (D-Rd) Cohorts (ASH 2020) - "A formulation of DARA for subcutaneous administration (DARA SC) was developed (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]; ENHANZE® drug delivery technology, Halozyme, Inc.). With extended follow-up in the D-Rd and D-VMP cohorts, clinical activity was comparable to corresponding DARA IV-containing regimens (DARA IV plus Rd [POLLUX]; DARA IV plus VMP [ALCYONE]). A low incidence of IRRs and a short duration of administration were reported in the D-Kd cohort in PLEIADES."

P2 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Transplantation

Subcutaneous Daratumumab Plus Standard Treatment Regimens in Patients with Multiple Myeloma across Lines of Therapy: Pleiades Study Update (ASH 2019) - "This phase 2, open-label, multicenter study (PLEIADES) assessed the efficacy and safety of DARA SC combined with bortezomib, lenalidomide, and dexamethasone (D-VRd) and bortezomib, melphalan, and prednisone (D-VMP) in patients with NDMM, and combined with lenalidomide and dexamethasone (D-Rd) in patients with RRMM...The PK of DARA SC and each regimen was consistent with historical data and immunogenicity of DARA and rHuPH20 were comparable to previous reports. With longer follow-up, DARA SC in combination with standard-of-care regimens demonstrated comparable clinical activity and safety to corresponding DARA IV regimens, with considerably lower IRR rates and substantially shorter durations of administration."

Clinical • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Subcutaneous daratumumab (DARA) in patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Part 2 update of the open-label, multicenter, dose escalation phase 1b study (PAVO). (ASCO 2018) - P1b; "The phase 1b PAVO study (NCT02519452) demonstrated that delivery of DARA with recombinant human hyaluronidase enzyme (rHuPH20) by subcutaneous (SC) infusion through a syringe pump (Part 1) or by manual SC injection (Part 2) was well tolerated with an efficacy profile consistent with IV DARA (Chari A, et al. DARA SC, which enables dosing in 3-5 minutes, was well tolerated with low IRR rates, had an acceptable PK profile, and demonstrated clinical response rates similar to DARA-IV. Updated data based on longer follow-up will be presented at the meeting."

Clinical • P1 data • Multiple Myeloma

Subcutaneous daratumumab (DARA SC) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients (Pts) with newly diagnosed amyloid light chain (AL) amyloidosis: Safety run-in results of andromeda. (ASCO 2018) - P3; "In the safety run-in, pts received a concentrated co-formulation of DARA (1,800 mg in 15 mL) and recombinant human hyaluronidase enzyme (rHuPH20; 30,000 U) in a single, pre-mixed vial, given by manual SC injection qw in Cycles 1-2, q2w in Cycles 3-6, and q4w thereafter 2 y. Cy 300 mg/m2 PO or IV and Bor 1.3 mg/m2 SC were given on Days 1, 8, 15, 22 of each 28-day cycle for 6 cycles and D 40 mg was given qw. DARA-CyBorD is tolerable in pts with AL amyloidosis with a low IRR rate and no new safety signals. The limited incidence of dyspnea and peripheral edema indicate a low risk for volume overload. Randomization into ANDROMEDA has begun."

Clinical • Oncology

A Phase 1b study of PEGPH20 plus pembrolizumab in patients with selected hyaluronan-high solid tumors (AACR 2017) - P1b; "Additional prophylaxis with piroxicam (possible musculoskeletal events) and proton pump inhibitors are given to all patients.Secondary endpoints are duration of response, disease control rate, progression-free survival per RECIST and immune-related response criteria, pharmacokinetics, and adverse events. Exploratory endpoints include secondary efficacy endpoints by PD-LI status, plasma and tumor HA levels, and imaging parameters of tumor blood flow (dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]) and tumor metabolic activity (positron emission tomography/computed tomography [PET/CT] scans)."

P1 data • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Venous Thromboembolism

Subcutaneous Delivery of Daratumumab in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM): Pavo, an Open-Label, Multicenter, Dose Escalation Phase 1b Study (ASH 2017) - P1b; "Introduction: Daratumumab (DARA), a CD38-targeted human monoclonal antibody, is approved as monotherapy and in combination with bortezomib (proteasome inhibitor; PI) or immunomodulatory drugs (IMiD; lenalidomide or pomalidomide) in pts with RRMM... SC administration of DARA + rHuPH20 was well tolerated, with lower than expected rates of IRRs in all groups, but particularly in those treated with DARA SC 1800 mg administered over only 3-5 minutes. Planned phase 3 studies will use DARA SC at the dose identified in Part 2."

Clinical • P1 data • Biosimilar • Dermatology • Inflammation • Multiple Myeloma

DRAMMATIC: S1803, Daratumumab/rHuPh20 +/- Lenalidomide as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration (clinicaltrials.gov) - P3; N=1100; Recruiting; Sponsor: Southwest Oncology Group

Clinical • New P3 trial • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

SUBCUTANEOUS DARATUMUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA: PART 2 UPDATE OF THE OPEN-LABEL, MULTICENTER, DOSE ESCALATION PHASE 1B STUDY (PAVO) (EHA 2018) - P1b; "The phase 1b PAVO study (NCT02519452) demonstrated that delivery of DARA with recombinant human hyaluronidase enzyme (rHuPH20) by subcutaneous (SC) infusion through a syringe pump (Part 1) or by manual SC injection (Part 2) was well tolerated with an efficacy profile consistent with IV DARA (Chari A, et al. DARA SC, which enables dosing in 3-5 minutes, was well tolerated with low IRR rates, had an acceptable pharmacokinetic profile, and demonstrated clinical response rates similar to DARA IV. Updated data based on longer follow-up will be presented at the meeting."

Clinical • P1 data • Multiple Myeloma

Subcutaneous Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma: Part 2 Safety and Efficacy Update of the Open-Label, Multicenter, Phase 1b Study (PAVO) (ASH 2018) - P1b, P3; "...To determine whether the duration of infusion can be shortened without compromising the safety or efficacy of daratumumab, an open-label, multicenter, phase 1b clinical trial (PAVO; NCT02519452) was conducted to evaluate a subcutaneous (SC) formulation of DARA with recombinant human hyaluronidase enzyme PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.) in patients with RRMM...Pre- and/or post infusion medications included acetaminophen, diphenhydramine, montelukast, and methylprednisolone...Over 50% of patients responded to treatment and median PFS has not been reached after median follow-up of 6.5 months. These data inform ongoing phase 3 studies of DARA SC in RRMM (including a non-inferiority study of DARA SC vs DARA IV [COLUMBA; NCT03277105]), smoldering multiple myeloma, and AL amyloidosis."

Clinical • P1 data • Biosimilar • Dermatology • Dermatopathology • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Immunology • Inflammation • Multiple Myeloma • Oncology • Pain

Subcutaneous daratumumab (DARA) in patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Part 2 update of the open-label, multicenter, dose escalation phase 1b study (PAVO). (ASCO 2018) - P1b; "The phase 1b PAVO study (NCT02519452) demonstrated that delivery of DARA with recombinant human hyaluronidase enzyme (rHuPH20) by subcutaneous (SC) infusion through a syringe pump (Part 1) or by manual SC injection (Part 2) was well tolerated with an efficacy profile consistent with IV DARA (Chari A, et al. DARA SC, which enables dosing in 3-5 minutes, was well tolerated with low IRR rates, had an acceptable PK profile, and demonstrated clinical response rates similar to DARA-IV. Updated data based on longer follow-up will be presented at the meeting."

Clinical • P1 data • Multiple Myeloma

Pharmacokinetics (PK) of Subcutaneous Daratumumab in Patients with Relapsed or Refractory (RR) Multiple Myeloma (MM): Primary Clinical Pharmacology Analysis of the Open-Label, Multicenter, Phase 1b Study (PAVO) (ASH 2018) - "Immunogenicity of DARA and rHuPH20 was similar to previous experience. These data validated the dose selection of 1,800 mg for ongoing phase 3 clinical trials of DARA SC in MM, smoldering MM, and amyloidosis."

Clinical • P1 data • PK/PD data • Biosimilar • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

SUBCUTANEOUS DARATUMUMAB + CYCLOPHOSPHAMIDE, BORTEZOMIB, AND DEXAMETHASONE (CYBORD) IN PATIENTS WITH NEWLY DIAGNOSED AMYLOID LIGHT CHAIN (AL) AMYLOIDOSIS: UPDATED SAFETY RUN-IN RESULTS OF ANDROMEDA (EHA 2019) - P3; "In the safety run-in, patients received DARA (1,800 mg in 15 mL) co-formulated with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.) administered subcutaneously (SC) qw Cycles 1-2, q2w Cycles 3-6, and q4w thereafter for ≤2 y. Cy 300 mg/m2 PO or IV, Bor 1.3 mg/m2 SC, and D 40 mg were administered qw ≤6 cycles. Two patients (7%) experienced infusion related reactions, all of which were grade 1.Conclusion DARA-CyBorD provides high overall hematologic response and CR rate in patients with newly diagnosed AL amyloidosis with a well-tolerated safety profile. Enrollment into the randomized portion of ANDROMEDA is ongoing. "

Clinical • Amyloidosis • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Renal Disease

RANDOMIZED, OPEN-LABEL, NON-INFERIORITY, PHASE 3 STUDY OF SUBCUTANEOUS (SC) VERSUS INTRAVENOUS (IV) DARATUMUMAB (DARA) ADMINISTRATION IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA: COLUMBA (EHA 2019) - P1b, P3; "In a phase 1b trial (PAVO, NCT02519452), a SC co-formulation of DARA with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.) was well tolerated.Aims Determine the efficacy, pharmacokinetics (PK), and safety of DARA SC vs DARA IV in patients (pts) with RRMM in the phase 3, randomized, open-label, multicenter, non-inferiority study COLUMBA (NCT03277105).Methods DARA SC (1,800 mg DARA + rHuPH20 [2,000 U/mL]) and DARA IV (16 mg/kg IV infusion) were given in 28-day cycles: QW Cycles 1-2, Q2W Cycles 3-6, and Q4W thereafter until disease progression or unacceptable toxicity. DARA SC had an improved safety profile with a significantly decreased IRR rate and a very short administration time. DARA SC is under investigation in ongoing phase 2 and 3 studies in MM and AL amyloidosis."

Clinical • Head-to-Head • P3 data

Randomized Phase 2 Study of Subcutaneous Daratumumab Plus Carfilzomib/Dexamethasone Versus Carfilzomib/Dexamethasone Alone in Patients with Multiple Myeloma Who Have Been Previously Treated with Intravenous Daratumumab to Evaluate Retreatment (LYNX) (ASH 2019) - P2; "Patients in the D-Kd group will also receive daratumumab SC (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc.]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. Secondary endpoints include overall response rate, rate of patients achieving complete response or better, progression-free survival, overall survival, overall MRD-negativity rate, time to next treatment, pharmacokinetics, and safety. The ClinicalTrials.gov identifier is NCT03871829."

Clinical • P2 data

Daratumumab (DARA) Plus Lenalidomide Versus Lenalidomide Alone As Maintenance Treatment in Patients with Newly Diagnosed Multiple Myeloma (NDMM) after Frontline Autologous Stem Cell Transplant (ASCT): Use of Minimal Residual Disease (MRD) As a Novel Primary Endpoint in the Phase 3 Auriga Study (ASH 2019) - P3; "Patients in the DARA plus lenalidomide arm will receive DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc.]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. Secondary endpoints include overall MRD-negativity rate at any time, duration of MRD negativity, rate of complete response or better (≥CR), duration of ≥CR, PFS, OS, health-related quality of life, and safety. The ClinicalTrials.gov identifier is NCT03901963."

Clinical • IO biomarker • P3 data • Residual disease • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • CD38

[VIRTUAL] CORTICOSTERIOD TAPERING IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA RECEIVING SUBCUTANEOUS DARATUMUMAB (DARA SC): PART 3 OF THE OPEN-LABEL, MULTICENTER, PHASE 1B PAVO STUDY (EHA 2020) - "In Part 2 of PAVO, DARA SC, a concentrated, pre-mixed subcutaneous (SC) co-formulation of daratumumab and recombinant human hyaluronidase PH20 (rHuPH20), was well tolerated, with a low infusion-related reaction (IRR) rate, and showed consistent serum concentrations and similar efficacy to DARA IV in patients with relapsed or refractory multiple myeloma (RRMM)...Patients received a 3-week tapering schedule (corticosteroid-free by Cycle [C] 1 Day [D] 22), with methylprednisolone given orally (PO)/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg; C1D15, 30 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day; C1D15, 20 mg for 1 day), or a 2-week tapering schedule (corticosteroid-free by C1D15), with methylprednisolone given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day)...Conclusion Rapid corticosteroid tapering over 2 weeks is safe in patients with RRMM receiving DARA SC. These data help guide future DARA SC..."

Clinical • P1 data • Cardiovascular • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pain • Respiratory Diseases

Subcutaneous daratumumab (DARA SC) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients (Pts) with newly diagnosed amyloid light chain (AL) amyloidosis: Safety run-in results of andromeda. (ASCO 2018) - P3; "In the safety run-in, pts received a concentrated co-formulation of DARA (1,800 mg in 15 mL) and recombinant human hyaluronidase enzyme (rHuPH20; 30,000 U) in a single, pre-mixed vial, given by manual SC injection qw in Cycles 1-2, q2w in Cycles 3-6, and q4w thereafter 2 y. Cy 300 mg/m2 PO or IV and Bor 1.3 mg/m2 SC were given on Days 1, 8, 15, 22 of each 28-day cycle for 6 cycles and D 40 mg was given qw. DARA-CyBorD is tolerable in pts with AL amyloidosis with a low IRR rate and no new safety signals. The limited incidence of dyspnea and peripheral edema indicate a low risk for volume overload. Randomization into ANDROMEDA has begun."

Clinical • Oncology