On June 10, 2022 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it is presenting new long-term follow-up results and subanalyses from clinical trials of its approved therapies, as well as data on investigational medicines from its broad blood cancer portfolio, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress in Vienna (Press release, Hoffmann-La Roche, JUN 10, 2022, View Source [SID1234616240]). Data include five-year results from the phase III CLL14 study of fixed-duration Venclexta/Venclyxto (venetoclax) plus Gazyva/Gazyvaro (obinutuzumab) in previously untreated chronic lymphocytic leukaemia (CLL); the final analysis of the phase III GALLIUM study of Gazyva/Gazyvaro plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the phase III POLARIX study of Polivy (polatuzumab vedotin) in combination with MabThera/Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Roche will also present data from its T-cell engaging bispecific antibody development programmes including Lunsumio (mosunetuzumab) and glofitamab in patients receiving later lines of therapy for non-Hodgkin lymphoma (NHL) and investigational medicines cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).

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"Blood cancers remain challenging to treat at all stages, but by improving frontline treatment options we aim to increase the likelihood of meaningful clinical outcomes for these patients," said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

Improving clinical outcomes with effective frontline treatment options
Five-year results of phase III CLL14 study of Venclexta/Venclyxto plus Gazyva/Gazyvaro (Abstract #S148)
After a median of 65.4 months following treatment with Venclexta/Venclyxto plus Gazyva/Gazyvaro, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta/Venclyxto plus Gazyva/Gazyvaro and 27.0% with Gazyva/Gazyvaro plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta/Venclyxto plus Gazyva/Gazyvaro arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed.[1] The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

Final analysis of phase III GALLIUM study of Gazyva/Gazyvaro (Abstract #S206)
After eight years of follow-up in people with previously untreated FL, a meaningful improvement in PFS was maintained with Gazyva/Gazyvaro plus chemotherapy, confirming its role as a standard of care for first-line treatment. Seven-year investigator-assessed PFS was significantly improved with Gazyva/Gazyvaro plus chemotherapy (63.4%) compared with MabThera/Rituxan plus chemotherapy (55.7%; HR 0.77; 95% CI: 0.64-0.93; p=0.006). This translated into a longer time to next anti-lymphoma treatment. At seven years, 74.1% of patients receiving Gazyva/Gazyvaro plus chemotherapy had not started new anti-lymphoma therapy compared to 65.4% receiving MabThera/Rituxan plus chemotherapy (HR 0.71; 95% CI: 0.58–0.87; p=0.001). The incidence of serious adverse events was 48.9% with Gazyva/Gazyvaro plus chemotherapy and 43.4% with MabThera/Rituxan plus chemotherapy.[2]

Subgroup analyses of pivotal phase III POLARIX study (Abstract #P1192)
Exploratory subgroup analyses of the phase III POLARIX study of Polivy with R-CHP compared to the current standard of care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL further support the potential for Polivy to transform the standard of care for people with this aggressive type of lymphoma. One of the datasets being presented is an analysis of study participants from Asia (China, Hong Kong, Japan, South Korea and Taiwan). Among this subgroup, results showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP, reducing the risk of disease progression, relapse or death by 36% (HR 0.64; 95% CI: 0.40-1.03). The safety profile was generally comparable for both regimens.[3]

Based on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL.

Providing novel bispecific antibodies for patients receiving later lines of therapy in lymphoma and beyond
Pivotal data from phase II NP30179 expansion study of glofitamab (Abstract #S220)
The pivotal phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients.[4] These data were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year.

Subgroup analysis and Lunsumio retreatment from pivotal phase II GO29781 study (Abstracts #P1126 and #P1124)
An exploratory subgroup analysis showed Lunsumio could be an efficacious and tolerable option in patients aged <65 and ≥65 years who had R/R FL and had received two or more prior therapies. Patients ≥65 years old achieved a higher objective response rate (ORR) than those <65 years old (87.0% vs 77.0%, respectively). Lower rates of CRS and serious adverse events were observed in patients ≥65 years old (37%) compared to those <65 years old (52%).[5] Additional data from the GO29781 study showed that retreatment with Lunsumio in patients who achieved a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with initial treatment.[6]

The EC recently approved Lunsumio for the treatment of people with R/R FL who have received at least two prior systemic therapies.

The data being presented at EHA (Free EHA Whitepaper), as well as phase III studies currently underway, will expand the understanding of glofitamab and Lunsumio and their impact in both later and earlier lines of treatment, with the aim of providing robust and durable treatment outcomes for people with different types of lymphomas.

Early data from novel investigational bispecific antibodies in R/R MM (Abstracts #P962 and #S180)
In line with Roche’s commitment to improving outcomes and personalising care for people with blood cancer, the company has expanded beyond lymphoma and leukaemia, evaluating two investigational medicines in MM. This is the third most common type of blood cancer, diagnosed in more than 170,000 people around the world each year and involves plasma cells (antibody-producing cells in the bone marrow).[7,8] Although advances in treatment have improved outcomes, MM remains an incurable disease characterised by multiple relapses, with an overall five-year survival rate of about 55%.[9] Roche is presenting data at EHA (Free EHA Whitepaper) on cevostamab, an investigational FcRH5xCD3 T-cell engaging bispecific antibody that is being evaluated as a monotherapy and in combination with other medicines to treat people with R/R MM, and on RG6234, a novel GPRC5DxCD3 T-cell engaging bispecific antibody that is being studied in a phase I trial in people with R/R MM. While early, the clinical activity and safety profiles observed with these molecules look encouraging and support further exploration.[10,11]

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood cancers.

In the US, Venclexta has been granted six Breakthrough Therapy Designations by the U.S. Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL, two for previously untreated acute myeloid leukaemia, and one for myelodysplastic syndromes.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body’s immune system. Gazyva/Gazyvaro is part of a collaboration between Roche and Biogen.

In the US, Europe and multiple other countries, Gazyva/Gazyvaro is currently approved in combination with chlorambucil for patients with previously untreated chronic lymphocytic leukaemia (CLL). It is also approved in combination with bendamustine, followed by Gazyva/Gazyvaro maintenance for the treatment of follicular lymphoma (FL) patients who did not respond to a MabThera/Rituxan (rituximab)-containing regimen, or whose FL returned after such treatment and in combination with chemotherapy for previously untreated advanced FL.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies.[12,13] Polivy is designed to bind to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.[14,15] Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

About Roche’s investigational CD20xCD3 bispecifics in haematology
Roche is currently developing two CD20xCD3 T-cell engaging bispecific antibodies, Lunsumio (mosunetuzumab) and glofitamab, designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Lunsumio and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats in order to identify those that maximise potential clinical benefits for patients. Lunsumio has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format that we call ‘2:1,’ which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions that bind to CD20 and one ‘Fab’ region that binds to CD3. The clinical development programmes for Lunsumio and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines for the treatment of people with CD20-positive B cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma.

On June 10, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive initial data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) (Press release, Cogent Biosciences, JUN 10, 2022, View Source [SID1234615864]). The data are being presented today in a poster presentation at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Vienna, Austria.

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"Advanced systemic mastocytosis is a severe, debilitating hematologic disorder and physicians and patients remain in search of more effective and better tolerated treatment options to fight this disease," said Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and APEX clinical trial investigator. "I am very impressed with the early, encouraging results presented today from the APEX study. If results like these can be shown in a larger set of patients with AdvSM, I believe bezuclastinib has the potential to help us take a big step forward in treating systemic mastocytosis patients."

"We are very excited to present initial clinical data from the APEX study of bezuclastinib in advanced systemic mastocytosis," said Andrew Robbins, Chief Executive Officer at Cogent Biosciences. "These results reinforce the hypothesis that a potent, selective KIT D816V inhibitor with limited CNS penetration has the potential to provide meaningful clinical activity to all systemic mastocytosis patients, without the tolerability challenges seen with other available treatment options. Based on these results, we expect to accelerate our timelines and investment and look forward to providing another APEX clinical update by the end of 2022, and to presenting SUMMIT clinical data in non-advanced systemic mastocytosis (NonAdvSM) patients in the first half of 2023."

Data from Ongoing Phase 2 APEX Clinical Trial

APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. As of the data cutoff date of May 24, 2022, 11 patients had been treated in Part 1 at one of four dose levels

(50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). The median age of patients at study entry was 70 years (ranging from 48-87 years). Patients were enrolled with the following sub-types: two patients with aggressive systemic mastocytosis (ASM), eight patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and one patient with mast cell leukemia (MCL). Two patients had received prior avapritinib and midostaurin treatment.

Initial Safety Data

As of the cutoff date, May 24, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and seen in no more than one patient with one serious adverse event and no Grade 4 events reported. Grade 3 events reported as at least possibly related were anemia (1 patient), neutropenia (1 patient) and hypersensitivity/mediator flare (1 patient). There were no reported cases of periorbital/peripheral edema, cognitive effects or intracranial bleeding events, which have been associated with other KIT inhibitors. As of the cutoff date, all patients remained on study. Subsequently, one SM-AHN patient with chronic myelomonocytic leukemia (CMML) transformed to acute myeloid leukemia (AML) and discontinued participation in the trial.

Initial Clinical Activity Data

As of the data cutoff date of May 24, 2022, all 11 patients treated were evaluated for signs of clinical activity. Eight of 11 patients had been treated for at least two cycles, had available data from bone marrow biopsy, and were evaluated for additional endpoints Cycle 3 Day 1 (C3D1) evaluable.

11/11 patients achieved ≥50% reduction in serum tryptase levels by central assessment

89% median reduction in serum tryptase

Six of these patients achieved reduction to <20 ng/mL

8/8 patients (C3D1 evaluable) achieved ≥50% reduction in bone marrow mast cells by central review

Six of these patients achieved complete clearance of bone marrow mast cell aggregates

8/8 patients (C3D1 evaluable) demonstrated decreases in KIT D816V variant allele fraction (VAF) by droplet digital polymerase chain reaction (ddPCR)

All patients remained on treatment with treatment duration ranging from 0.5 – 4.8 months

Two patients enrolled had previously received and discontinued avapritinib for toxicity reasons (intracranial hemorrhage, thrombocytopenia). Both patients have demonstrated clinical outcomes consistent with the avapritinib-naïve patients, including similar magnitude reductions in serum tryptase.

Bezuclastinib Clinical Development

Based on the favorable initial safety and tolerability profile and clinical activity observed to date in the Phase 2 APEX clinical trial with bezuclastinib for AdvSM, Cogent will continue enrolling patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the trial. A pre-planned interim analysis is scheduled once approximately 28 patients have received at least two cycles of study treatment in Part 1. Cogent plans to present additional data from APEX by the end of 2022. In addition, Cogent continues to actively enroll patients in SUMMIT, a Phase 2 clinical trial with bezuclastinib for NonAdvSM, and PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with imatinib-resistant Gastrointestinal Stromal Tumors (GIST). Cogent plans to present initial data from SUMMIT and lead-in data from PEAK in the first half 2023.

Conference Call Information & EHA (Free EHA Whitepaper) poster

Cogent will host a webcast today at 8:00 am ET to discuss today’s APEX results. The webcast will be accessible through the Investors and Media section of Cogent’s website at View Source Following the live webcast, an archived replay will also be available.

The APEX poster to be presented at EHA (Free EHA Whitepaper) is available to registered conference attendees as well as on the Cogent Biosciences website in the Posters and Publications section of www.cogentbio.com/research.

On June 10, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster presentation of preclinical and clinical data on VIP152, the Company’s PTEFb/CDK9 inhibitor, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress, being held virtually and in Vienna, Austria from June 9-12, 2022 (Press release, Vincerx Pharma, JUN 10, 2022, View Source [SID1234615882]).

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The EHA (Free EHA Whitepaper) poster presents data from a high-grade B-cell lymphoma (HGBL) patient with a treatment-related decrease in circulating tumor TP53 mutation and preclinically demonstrates sensitivity of cells derived from chronic lymphocytic leukemia (CLL) patients relapsed after ibrutinib and venetoclax to VIP152 regardless of their TP53 mutation status. "In a pooled analysis of 57 patients with solid or hematologic malignancies, our findings demonstrate that VIP152 did not prolong the QTc interval, which is indicative of a favorable cardiac safety profile and clearly differentiates CDK9 inhibition from the recently reported cardiac toxicity of MCL1 inhibitors," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "Compared with other CDK9 inhibitors, VIP152 was the most selective CDK9 inhibitor and had the most robust MYC mRNA downregulation. We believe the high selectivity of VIP152 affords a manageable safety profile, based on the overall patient safety data we shared earlier this week. Additionally, our data showed reproducible reductions in MYC, MCL1, and PCNA mRNA in the blood of patients with various types of lymphoma after VIP152 treatment. These data support the utility of a selective CDK9 inhibitor for the treatment of patients with hematologic malignancies," added Dr. Hamdy.

The EHA (Free EHA Whitepaper) poster also shares new data for 5 lymphoma patients: 3 with HGBL, 1 double expressor diffuse large B-cell lymphoma (DLBCL) and 1 CLL patient from 2 ongoing phase 1 trials. The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. "Two patients with double-hit DLBCL achieved complete remission for 3.5 and 2.5 years and have remained in remission nearly two years after stopping therapy. In addition, the first patient with CLL—who had failed BTK inhibitors and venetoclax—to be treated with a low dose (15 mg) of VIP152 showed initial evidence of clinical activity by physical exam and laboratory parameters," added Dr. Hamdy. "VIP152 also showed a favorable safety profile in lymphoma patients, with manageable neutropenia. The once-weekly VIP152 dosing regimen continues to allow for recovery of neutrophils before the next dose. The results presented at EHA (Free EHA Whitepaper), combined with the totality of preclinical and clinical data generated in our programs to date, support our recent strategic decision to prioritize our VIP152 clinical program on double-hit DLBCL and CLL. We continue to be excited about VIP152 and look forward to advancing our development program with the goal of delivering new treatment options for these patients."

Key Presentation Highlights:

Poster presentation, titled, "VIP152 is a novel CDK9 inhibitor with improved selectivity, target modulation, and cardiac safety in patients with lymphoma," presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

A KINOMEscan assay revealed a range of ‘hits’ with VIP152 compared with other CDK9 inhibitors (fadraciclib, alvocidib, KB-0742, and AZD4573). In depth evaluation of all potential hits was performed by Kd determination. Kd values showed VIP152 as the most selective CDK9 inhibitor in the clinic today. In the presence of low ATP, VIP152 has an IC50 value of 4.5 nM, and low nanomolar potency was also maintained in the presence of high ATP. The VIP152 IC50 of 4.5 nM was maintained for 15 to 20 hours in the plasma of patients treated at the current clinical dose of 30 mg. Therefore, VIP152 is a highly potent inhibitor of CDK9 kinase activity even in the presence of high ATP concentrations. These data show that physiologically relevant levels of VIP152 are achieved in patients with the 30-mg dose.
In vitro VIP152 treatment led to the most robust downregulation of MYC mRNA expression, observed by a downregulation of 85% genes in two DLBCL cell lines, SU-DHL-4 and SU-DHL-10, compared with atuveciclib (76%) and KB-0742 (68%).
Pooled cardiac safety data from 57 patients demonstrated that VIP152 does not prolong QTc interval after single or multiple doses (5-30 mg).
VIP152 cytotoxicity was evaluated in CRISPR/Cas9 edited CLL cells with homozygous TP53 mutations and showed that wild type and TP53 mutant cell lines were sensitive to VIP152 treatment at 0.5 and 1.0 µM. In vitro treatment of CLL patient-derived cells showed a concentration-dependent reduction in cell viability regardless of number of lines of prior therapy including cells from patients who had relapsed or were refractory to ibrutinib or venetoclax therapy.
This presentation includes new data from five patients (n=3 with HGBL, n=1 double-hit DLBCL, and n=1 CLL). The safety, treatment duration, pharmacokinetics (PK), and progressive disease (PD) were pooled with 7 previously reported HGBL patients for a total of 12 lymphoma patients shown in the presentation. Duration of treatment for this cohort ranges from 2 weeks to over 3 years. Of the 12 total treated patients, five were evaluable for best overall response. Of these, two patients with double-hit DLBCL achieved complete remission and remain in remission nearly two years after stopping therapy, while others stopped treatment due to clinical or radiographic progression; and, in one case due to investigator decision.
The absolute neutrophil count was measured at each treatment visit. Our data show that once weekly dosing of VIP152 allows for the recovery of neutrophils before the next dose. Neutropenia was considered monitorable and manageable with supportive care.
Blood-based PD effect showed a robust down-modulation of MYC, MCL1 and PCNA mRNA in all 11 patients analyzed. Circulating tumor DNA (ctDNA) changes were monitored in three newly reported patients. In one patient, ctDNA reduction in TP53 mutation, and in CDK6 and MYC copy number was observed after three weeks of VIP152 treatment. ctDNA is currently being investigated as a non-invasive tool to aid with predicting outcomes to treatment in patients with high-risk B-cell lymphoma (Meriranta Blood 2022).
Clinical evaluation of VIP152 is currently ongoing in two phase 1 trials in patients with solid tumors or aggressive NHL (NCT02635672), and with CLL and Richter Syndrome (NCT04978779). The poster can be accessed on the presentations section of the Vincerx website.

On June 10, 2022 Amgen (NASDAQ:AMGN) reported that it will present at the Goldman Sachs 43rd Annual Healthcare Conference at 1:40 p.m. ET on Wednesday, June 15, 2022 (Press release, Amgen, JUN 10, 2022, View Source [SID1234615900]). David M. Reese, M.D., executive vice president of Research and Development and Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On June 10, 2022 Zai Lab Limited, a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted two Breakthrough Therapy Designations for investigational repotrectinib for the treatment of patients with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and one prior line of platinum-based chemotherapy (EXP-2) and for those with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and no chemotherapy or immunotherapy (EXP-4) (Press release, Zai Laboratory, JUN 10, 2022, View Source [SID1234633496]). The Breakthrough Therapy Designations for repotrectinib were supported by the data from both global and Chinese TKI-pretreated ROS1-positive NSCLC patients enrolled in the Phase 1/2 TRIDENT-1 study.

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"Since repotrectinib received Breakthrough Therapy Designation by the CDE earlier this year for ROS1-positive TKI-naïve patients, today’s recognition further supports repotrectinib as a potential best-in-class treatment for ROS1-positive NSCLC in both TKI-naïve and pretreated patients in China," said Alan Sandler, M.D., President and Head of Global Development, Oncology at Zai Lab. "There remain significant unmet needs for ROS1-positive NSCLC patients, and we look forward to our continued partnership with regulatory authorities in China to bring this important medicine to patients in need as soon as possible."

The Breakthrough Therapy Designation review policy is designed to facilitate the development and expeditious review of novel medicines that are intended for the prevention or treatment of serious, life-threatening diseases or diseases that severely impact the quality of life for which there is no existing treatment, or where sufficient evidence indicates advantages of the novel drug over currently available treatment options. Drugs granted Breakthrough Therapy Designations receive priority communications and guidance from the CDE to promote and expedite the drug development process.

Lung cancer is both the most commonly diagnosed cancer type and the leading cause of cancer death in China. The incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths1. NSCLC accounts for approximately 85% of lung cancer, and about 70% of NSCLC is locally advanced or metastatic at initial diagnosis. In China, ROS1 rearrangements occur in 2-3% of patients with advanced NSCLC.

1Globocan 2020.

About Repotrectinib

Repotrectinib is a next-generation kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of NSCLC and advanced solid tumors. Tumors with mutations to their ROS1 and NTRK genes have a higher likelihood of developing resistance to existing targeted therapies. In many cases, these mutations prevent existing medicine from targeting and binding to the tumor as effectively as tumors that do not carry the mutations. Repotrectinib is designed to be smaller and less bulky than existing targeted therapies and may circumvent some of the resistance mechanisms found in tumors with ROS1 and NTRK mutations. Zai Lab and Turning Point Therapeutics, Inc. are studying repotrectinib in TRIDENT-1, a registrational Phase 1/2 study in adults, and CARE, a Phase 1/2 study in pediatric patients. The compound has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. Zai Lab is enrolling patients in the registrational Phase 2 portion of TRIDENT-1 in Greater China, while Turning Point Therapeutics is enrolling patients in other regions of the world.

Repotrectinib has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration in: ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs, with or without prior chemotherapy, and have no satisfactory alternative treatments; and ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy. Additionally, repotrectinib was previously granted four Fast-Track designations in: ROS1-positive advanced NSCLC patients who are ROS1 TKI naïve; ROS1-positive advanced NSCLC patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior ROS1 TKI; ROS1-positive advanced NSCLC patients pretreated with one prior ROS1 TKI without prior platinum-based chemotherapy; and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments. Repotrectinib was also granted an Orphan Drug designation in 2017.

Zai Lab has an exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China.