pinatuzumab vedotin (RG7593) / Roche, Pfizer - LARVOL DELTA

Efficacy and Safety of Polatuzumab Vedotin in Follicular Lymphoma: A Systematic Review of Clinical Trials (ASH 2023) - " In 5 trials (N=204), 13 patients with Pola + atezolizumab (Ate) + obinutuzumab (Obi), 49 patients with Pola + Obi + venetoclax (Ven), 39 patients with Pola + Obi, 62 with Pola + Obi + lenalidomide (Len), and 20 patients with Pola + rituximab (Rit)...(N=41), Pola + Rit was compared with pinatuzumab vedotin (Pina) + Rit... Pola was well tolerated by most of the patients with FL alone or in combination with Obi, Rit, Len, Ven. Pola had relatively better response and survival rates as compared to Pina in combination with Rit. In early phase clinical trials, three drug regimens of Pola and Obi with Ven, and Len were effective in the treatment of heavily pretreated follicular lymphoma."

Clinical • Review • Follicular Lymphoma • Hematological Malignancies • Lymphoma • CD79B

Monomethyl Auristatin E (MMAE), a Payload for Multiple Antibody Drug Conjugates (ADCs), Demonstrates Differential Red Blood Cell Partitioning Across Human and Animal Species. (PubMed, Xenobiotica) - "To test whether MMAE released from the ADC would show any difference in RBC partitioning, pinatuzumab vedotin or polatuzumab vedotin was administered to mice, rats, and monkeys. In vivo dosing of pinatuzumab vedotin in mouse displayed systemic MMAE at about a 5-fold higher blood concentration compared to plasma concentration once MMAE reached a pseudo-equilibrium, while systemic MMAE from blood and plasma concentration showed a 1.65-fold difference in rat.Implication and These data demonstrated that MMAE has a distinct RBC partitioning across different species, which may contribute to, at least in part, to the differential in the systemic MMAE levels observed in vivo between preclinical and clinical studies. These findings highlight the importance of fully characterizing the ADME properties of both the ADC and its payload, to enable better translation from animals to human for ADC development."

Journal

Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). (PubMed, Lancet Haematol) - P2; "R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit-risk favouring R-pola."

Clinical • Journal • P2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] New drugs for low grade lymphoproliferative diseases (EHOC 2020) - "For symptomatic patients or for those with high tumor burden, initial treatment is usually chemoimmunotherapy with an anti-CD20 monoclonal antibody (mo-Ab), most commonly Rituximab or Obinutuzumab plus an alkylator, such as bendamustine or chlorambucil and/or a pourine analog, such as fludarabine or cladribine...Newer anti-CD20 mo-Abs, such as Ublituximab appear equally effective, but have not yet been tested comparatively with the previous ones. Radioconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab are no more in broad use due to unpredicted myelotoxicity. The newer 90Y-epratuzumab tetratexan appears safe as consolidation following R-CHOP in DLBCL patients. Polatuzumab vedotin, Pinatuzumab vedotin and Tafasitamab targeting CD19 have mainly been used, combined with an anti-CD20 mo-Ab to treat RR-DLBCL with success, which render them candidates for indolent lymphomas also...Acalabrutinib, already approved for CLL/SLL and MCL, is now being tested for other..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatology • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CRBN • EZH2 • SYK

An anti-CD22-seco-CBI-Dimer ADC for the treatment of non-Hodgkin lymphoma that provides a longer duration of response than auristatin ADCs in preclinical models. (PubMed, Mol Cancer Ther) - "We are interested in developing a second generation of antibody-drug conjugates (ADCs) for the treatment of non-Hodgkin's lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule inhibiting ADCs pinatuzumab vedotin (anti-CD22-vc-MMAE) and polatuzumab vedotin (anti-CD79b-vc-MMAE). We found that anti-CD22-(LC:K149C)-SN36248 was effective in xenograft models resistant to pinatuzumab vedotin, gave a longer duration of response, had a different mechanism of resistance and was able to deplete normal B cells better than pinatuzumab vedotin. These studies provide evidence that anti-CD22-(LC:K149C)-SN36248 has the potential for longer duration of response and more efficacy in indolent NHL than MMAE ADCs and may provide the opportunity to improve outcomes for NHL patients."

Journal • Preclinical • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B

A Study of the Safety and Pharmacokinetics of Escalating Doses of DCDT2980S in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia And DCDT2980S in Combination With Rituximab in Patients With Relapsed... (clinicaltrials.gov) - P1; N=92; Active, not recruiting; Sponsor: Genentech, Inc.; Trial primary completion date: Dec 2015 ->Sep 2015

Trial primary completion date • Biosimilar • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

Seattle Genetics achieves milestones as Genentech advances two antibody-drug conjugates (ADCs) into phase II development (Seattle Genetics, Inc) - Seattle Genetics will receive undisclosed milestone payments under its antibody-drug conjugate (ADC) collaboration with Genentech; The milestones were triggered by Genentech’s advancement of two ADCs utilizing Seattle Genetics technology into phase II clinical development

Financing • Hematological Malignancies

Roche: Q1 2014 Sales Results (Roche) - Anticipated presentation of interim data from P2 ROMULUS RG7596 vs. RG7593 trial for non-Hodgkin's lymphoma at ASCO (May 30 - Jun 03, 2014); Anticipated initiation of P1 trial for refractory solid tumors in Apr 2014

Anticipated P2 data • Anticipated trial initiation date • Oncology

Seattle Genetics highlights data presentations from Genentech ADC collaborator programs at ASH Annual Meeting (ASH 2012, Seattle Genetics, Inc) - P1, N=99; NCT01209130; "Seattle Genetics...highlighted clinical data from two antibody-drug conjugate (ADC) programs in development by Genentech...The data were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. Among all 33 patients evaluable for efficacy, nine patients (27 percent) had an objective response to single-agent DCDT2980S. Among the 17 patients treated at doses greater than or equal to 1.8 mg/kg, seven patients (41 percent) had an objective response, including one complete response and six partial responses."

P1 data • Hematological Malignancies

Seattle Genetics highlights data presentations from Genentech ADC collaborator programs at ASH Annual Meeting (ASH 2012, Seattle Genetics, Inc) - P1, N=99; NCT01209130; "Seattle Genetics...highlighted clinical data from two antibody-drug conjugate (ADC) programs in development by Genentech...The data were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. Among all 33 patients evaluable for efficacy, nine patients (27 percent) had an objective response to single-agent DCDT2980S. Among the 17 patients treated at doses greater than or equal to 1.8 mg/kg, seven patients (41 percent) had an objective response, including one complete response and six partial responses."

P1 data • Hematological Malignancies

Preliminary results of a phase II randomized study (ROMULUS) of polatuzumab vedotin (PoV) or pinatuzumab vedotin (PiV) plus rituximab (RTX) in patients (Pts) with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) (ASCO 2014) - Presentation time: Saturday, May 31; 1:15 PM to 2:45 PM; Abstract #8519; P2, N=58; NCT01691898; Sponsor: Genentech; "Overall safety profiles of both regimens were similar. Tx-emergent adverse events (AE) >25%: fatigue (52%), diarrhea (42%), nausea (37%), peripheral neuropathy (PN) (32%), constipation (26%)....Similar efficacy was observed with both ADCs in heavily pretreated pts with DLBCL. The higher CR rate with PoV + RTX suggests greater clinical activity in R/R FL."

P2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Roche committed to innovation and growth (Roche) - P1, N=99; NCT01209130; Preliminary data for RG7593 will be presented at investor conference; The data indicate very promising anti-tumor activity in pts with relapsed or refractory disease following treatment with anti-CD20 containing therapies

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Roche: Late-Stage Pipeline Event (Roche) - "ADCs in hematology: Anti-CD22 and anti-CD79b: Phase I responses in multiple histologies"; "Anti-tumor responses observed by histology"

P1 data • Hematological Malignancies • Oncology

Roche: HY 2014 Results (Roche) - Anticipated NME submission in EU for hematological tumors in 2017 or later; Anticipated NME submission in US for hematological tumors in 2017 or later

Anticipated EU regulatory • Anticipated NDA • Oncology

ROMULUS: A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL) (clinicaltrials.gov) - P2; N=230; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion