[EHA First Look] An overview of the academic progress of Roche's blood R&D pipeline

The fragrant wheat in June is also the season of academic harvest; the 2021 ASCO annual meeting, EHA annual meeting and the 16th ICML conference are coming as scheduled, and many heavy researches will be here for the collision of ideas.

As an industry leader in the field of blood diseases, Roche announced a number of important research developments, and the editor will lead everyone to take a sneak peek.

Otuzumab has been approved in China, which will usher in a new era of type II anti-CD20 monoclonal antibody treatment.
The latest news.
Otuzumab has been officially approved by NMPA today for the treatment of newly treated follicular lymphoma patient.

As a new humanized anti-CD20 monoclonal antibody, its antibody-dependent cytotoxicity (ADCC) has been significantly enhanced.

Otuzumab has been approved for multiple indications abroad, and the approval in China will benefit more patients and open a new era of new anti-CD20 monoclonal antibody treatment for indolent lymphoma.

The CLL14 study updated the results of the 4-year follow-up: a median follow-up time of 52.
4 months, compared with the fixed-dose regimen of otuzumab combined with Bcl-2 inhibitor Ven-Obi in patients with newly treated chronic lymphocytic leukemia (CLL) The combination of otuzumab and chlorambucil (Clb-Obi) regimen showed a sustained progression-free survival (PFS) benefit (mPFS NR vs.
36.
4 months), which is in patients with different risk types Consistent in the population (including TP53 mutation/deletion patients, IGHV non-mutated patients).

Patients with mutations can still benefit from subsequent monotherapy with BTK inhibitors (EHA S146).

The results of another minimal residual disease (MRD) study showed that the Ven-Obi regimen can induce sustained deep remission, and the median MRD doubling time is also significantly longer (EHA-EP632).

Fast infusion of otuzumab, safe and tolerable: The GAZELLE study assessed that in patients with follicular lymphoma (FL), otuzumab was given a 90-minute rapid infusion (short- Duration infusion, SDI) safety.

The results showed that no new safety signals were found for rapid infusion (ASCO-7545/EHA-EP807).

LYSA Phase II clinical study: The triple regimen of Otuzumab+Venecla+Atelizumab in the treatment of patients with relapsed/refractory (R/R) FL/marginal zone lymphoma (MZL) has a good curative effect and Safety; FL cohort (n=58), with a median follow-up of 14.
5 months, overall response rate (ORR) was 53.
6%; MZL cohort (n=20), ORR was 66.
76%; no unexpected results were observed in the triple scheme Toxicity (ASCO-7544).

Antibody-drug conjugate polatuzumab can bring new breakthroughs in the treatment of NHL.
Polatuzumab (pola) is an antibody-drug conjugate targeting CD79b.
Based on its excellent efficacy, the Pola-BR program has been approved by the FDA in 2019 for the treatment of R/ R Patients with diffuse large B-cell lymphoma (DLBCL).

The results of the two studies announced at this year's EHA meeting continue to confirm the efficacy of the Pola-BR regimen, and other combination treatment regimens based on pola (Pola-R-Len) are also expected to help more DLBCL patients to be cured.

The current phase III clinical studies carried out by pola in China, including initial treatment and R/R DLBCL, have very exciting results.

A Phase Ib/2 study evaluated the efficacy of the new triple regimen Pola-R-Len in patients with R/R DLBCL.

The main analysis results showed that the best overall response rate (BOR) evaluated by the investigator was 74% (36/49), and the complete response (CR) rate was 35% (17/49); the combined treatment program has good safety .

It is hoped that this new chemotherapy-free regimen will help solve the unmet clinical needs of patients with R/R DLBCL (ASCO-7512).

The results of the Pola-BR regimen are still eye-catching: In a single-center prospective study of 26 patients, the ORR of the Pola-BR regimen for R/R non-Hodgkin’s lymphoma (NHL) was 61%, and the CR rate was 61%.
It is 46% (EHA-EP544).

In another retrospective study, patients with R/R high-grade lymphoma who received only pola-BR treatment and bridging CAR-T treatment groups achieved complete remission rates of 31% and 25%, respectively (EHA-EP555).

In addition to continuous progress in the field of DLBCL, this ASCO annual meeting also announced the results of pola combined with Otuzumab and Pola-G-Ven in R/R FL patients.

The safety of the triple regimen is consistent with the known safety profiles of the three single drugs.
After a median follow-up of 14.
4 months, the 12-month PFS rate was 73%, and mPFS has not yet reached (ASCO-7534).

Bispecific antibodies began to shine in the field of lymphoma.
Both Glofitamab (Glofit) and Mosunetuzumab (Mosun) are bispecific antibodies targeting CD20/CD3.
Based on Roche’s unique bi-antibody technology development platform, these two antibodies began to be used in The field of lymphoma is emerging.
Last year, the FDA granted Mosun a breakthrough therapy designation (BTD).

The two drugs are currently being developed as monotherapy and combined with other drug programs.
Following the release of relevant data at the ASH meeting last year, Glofit and Mosun have continued to work hard to determine the treatment options that maximize the benefits for patients.

GO41944 (NCT04408638) announced the trial design plan: This phase III, open-label, randomized trial aims to evaluate the efficacy and safety of the Glofit-GemOx regimen versus the R-GemOx regimen in the treatment of R/R DLBCL patients, and will also conduct pharmacokinetics Analysis of the dimensions of science and biomarkers.

The study plans to enroll 270 patients and is expected to be completed in March 2022 (ASCO-TPS7575).

Glofit monotherapy R/R NHL phase I dose escalation cohort updated data: data analysis as of December 1, 2020, for aggressive NHL (n=28), BOR and complete metabolic remission (CMR) rates were 64.
3% and 64.
3%, respectively.
57.
1%; At the same time, as the target dose increases, a trend of improvement in efficacy can be observed.

For inert NHL (n=24), BOR and CMR were 79.
2% and 70.
8%, respectively.

The updated data shows that among R/R NHL patients who failed multi-line therapy, Glofit monotherapy still showed strong anti-tumor activity; the main adverse events were CRS, mostly low-grade, and mainly occurred in the first cycle ( ASCO-7519/EHA-EP501).

The initial efficacy of Mosun combined with Pola regimen in the treatment of R/R NHL patients is good.
The early results of a dose escalation trial showed that the Mosun-pola regimen in the treatment of R/R NHL ORR was 68.
2% (15/22), and the CR rate was 54.
5% ( 12/22); and with acceptable safety, no CRS ≥2 levels have been observed.

(ASCO -7520/EHA-S222) Mosun single-agent first-line treatment of elderly/unfit DLBCL patients updated data: mosun single-agent therapy shows continuous efficacy and good safety.
For elderly patients who cannot tolerate standard immunochemotherapy regimens, mosun Provides a new option without chemotherapy (EHA-EP503).

The phase III multicenter randomized controlled study of Mosun combined with lenalidomide (M-Len regimen) versus R2 regimen in the treatment of R/R FL will be officially launched.
It is planned to enroll about 400 patients in 150 centers in 16 countries.
Patient 1: 1 Randomly receive 12 cycles of treatment with M-Len or R2 regimen, and the primary efficacy endpoint is PFS (EHA-PB1565) assessed by IRC.

The C5 complement inhibitor crovalimab has entered phase III research.
China's research and development is synchronized with the world.
Crovalimab is a new generation of C5 complement inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
It has undergone continuous monoclonal antibody recovery technology (Smart- Ig) It is engineered to have a long half-life and can be injected subcutaneously; the phase I/II COMPOSER trial demonstrated its superior efficacy and safety, which enabled crovalimab to enter the phase III clinical trial phase and began to recruit patients.

At this EHA annual meeting, crovalimab announced a number of research designs, including two important phase III clinical trials (COMMODORE 1, COMMODORE 2), respectively evaluating crovalimab versus eculizumab in the past, which has received C5 complement inhibitors.
And the efficacy and safety in PNH patients who have not received C5 complement inhibitor therapy.

In addition, multiple centers in mainland China are conducting COMMODORE 3 trials at the same time.
This single-arm study is to verify the efficacy and safety of crovalimab in PNH patients ≥12 years of age who have not previously received C5 complement inhibitor therapy (EHA PB1480).

In foreign countries, complement C5 inhibitors have become the standard treatment plan for PNH; however, this type of drug is not yet available in China, and clinical studies at home and abroad are currently being carried out simultaneously.
It is hoped that this plan can benefit domestic PNH patients more quickly.

The FcRH5/CD3 bispecific antibody Cevostamab may bring new hope to RRMM patients.
Cevostamab is a humanized, IgG-based T cell binding bispecific antibody that targets FcRH5 (Fc receptor homologous) on the surface of myeloma cells.
Thing 5) and CD3 on the surface of T cells form an effective immune synapse, thereby activating T cells to kill myeloma cells.

At the 2020 ASH annual meeting, Roche announced for the first time that cevostamab has shown encouraging activity in multi-line treatment of patients with relapsed/refractory multiple myeloma (RRMM) (GO39775, phase I clinical trial).
This EHA annual meeting Update the relevant results of the study again.

The biomarker evaluation results show that in patients who have obtained sufficient bone marrow samples, FcRH5 is expressed on the surface of myeloma cells, and the previous treatment plan and the number of treatment lines do not seem to affect the expression of FcRH5; in addition, combined with cytogenetic analysis, FcRH5 shows Out of the trend of high expression in high-risk patients, no correlation between baseline FcRH5 and treatment response was observed.

These results further confirm that FcRH5 is a promising target for RRMM therapy (EHA-EP965).

Poke "read the original text", we make progress together