On March 15, 2022 Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS), reported the presentation of positive results and biomarker analyses from the pivotal study "CHOICE-01" (clinicaltrials.gov identifier# NCT03856411), a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus chemotherapy as first-line treatment of advanced squamous or non-squamous non-small cell lung cancer ("NSCLC") (Press release, Coherus Biosciences, MAR 15, 2022, View Source [SID1234610111]). The final progression-free survival ("PFS") analysis confirms the finding of the previous interim PFS analysis, demonstrating a statistically significant and clinically meaningful improvement in PFS per RECIST v1.1 compared to chemotherapy alone. The study also demonstrated an improvement in overall survival ("OS") in a prespecified interim OS analysis. These results will be summarized later today during the ASCO (Free ASCO Whitepaper) Plenary Series, in an oral presentation by Professor Jie Wang, MD, PhD, from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. The abstract is now available on the ASCO (Free ASCO Whitepaper) website.

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"We are excited about the consistently strong clinical evidence that toripalimab has displayed across multiple tumor types," said Dr. Patricia Keegan, Chief Medical Officer at Junshi Biosciences. "The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as first-line therapy for advanced NSCLC patients without EGFR/ALK mutations."

"In the CHOICE-01 study in patients with non-small cell lung cancer, toripalimab has once again demonstrated the potential to delay disease progression and help patients live longer," said Theresa LaVallee, PhD, Chief Development Officer at Coherus. "The study investigators also reported interesting biomarker data with toripalimab plus chemotherapy having activity independent of PD-L1 expression as well as a statistically significant overall survival advantage in NSCLC patients who have alterations in the focal adhesion-PI3K-AKT signaling pathway, a finding which may inform the design of future toripalimab clinical trials."

About CHOICE-01
A total of 465 treatment-naïve advanced NSCLC patients without EGFR/ALK mutations were randomized (2:1): 309 to toripalimab plus chemotherapy (the "toripalimab arm") and 156 to placebo plus chemotherapy (the "placebo arm"). The primary endpoint was PFS assessed by the investigator. Secondary endpoints included PFS assessed by a blinded independent review committee ("BIRC"), OS and safety. Patients from the placebo arm were actively crossed over to toripalimab treatment upon disease progression.

As of October 31, 2021:

At the final analysis, a significant improvement in PFS was detected in the toripalimab arm over the placebo arm (hazard ratio ("HR")=0.49; 95% confidence interval ("CI"): 0.39-0.61, P<0.0001) with median PFS of 8.4 vs. 5.6 months. The 1-year PFS rates for the toripalimab and placebo arms were 36.7% and 17.2%, respectively.
PFS as assessed by BIRC was also significantly longer in the toripalimab arm.
A prespecified interim analysis demonstrated a statistically significant improvement in overall survival for the toripalimab arm over the placebo arm (median OS not reached vs. 17.1 months, HR = 0.69 (95% CI: 0.52-0.92)).
The PFS benefits were observed in patients treated with toripalimab plus chemotherapy across key subgroups, including histologic subtype and tumor PD-L1 expression.
Genomic analysis revealed a PFS benefit associated with high tumor mutation burden and with genetic alterations in the focal adhesion-PI3K-AKT and IL-7 pathways in patients treated with toripalimab plus chemotherapy.
The addition of toripalimab to standard first-line chemotherapy in patients with advanced NSCLC showed a manageable safety profile with no new safety signals observed. The incidence of Grade ≥3 adverse events (AEs) was 78.6% in the toripalimab arm vs. 82.1% in the placebo arm. AEs leading to discontinuation of toripalimab or placebo were 14.3% vs. 3.2%, respectively.
Junshi Biosciences and Coherus are evaluating potential registration avenues for toripalimab in combination with chemotherapy for the first-line treatment of advanced non-small cell lung cancer in the United States. In China, the supplemental New Drug Application for this indication was accepted in December 2021 by the National Medical Products Administration ("NMPA").

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promote the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.
In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are four approved indications for toripalimab in China:

unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma ("NPC") after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
The first three indications have been included in the National Reimbursement Drug List ("NRDL") (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma and NPC.

In addition, two supplemental New Drug Applications ("NDAs") for toripalimab are currently under review by the National Medical Products Administration ("NMPA") in China:

in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic ESCC.
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic NSCLC without EGFR or ALK mutations.
In the United States, the FDA has granted priority review for the toripalimab biologics license application ("BLA") for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. The FDA has assigned a Prescription Drug User Fee Act ("PDUFA") target action date for April 2022 for the toripalimab BLA. The FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC in 2021 as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC in 2020. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. In 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.

On March 15, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported financial results for the year and quarter ended December 31, 2021 (Press release, Gamida Cell, MAR 15, 2022, View Source [SID1234610127]). Net loss for 2021 was $89.8 million, compared to a net loss of $61.6 million in 2020. As of December 31, 2021, Gamida Cell had total cash and cash equivalents of $95.9 million.

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During the past quarter and into 2022, Gamida Cell:

Continued to advance omidubicel, a potentially life-saving cell therapy treatment for patients with blood cancers in need of stem cell transplant. In the first quarter of 2022, Gamida Cell initiated a rolling Biologics License Application (BLA) submission for omidubicel following the receipt of positive Type B meeting correspondence from the U.S. Food and Drug Administration (FDA).
Progressed activities to address the FDA’s clinical hold on the Investigational New Drug (IND) application for GDA-201, which was imposed based on FDA questions about donor eligibility procedures and assay qualification prior to the initiation of the study in patients with follicular and diffuse large B-cell lymphomas.
Advanced the company’s NAM-enabled natural killer (NK) cell pipeline, including targets GDA-301, GDA-501 and GDA-601, which focus on solid-tumor and hematological cancers. These targets utilize CAR, membrane bound- and CRISPR-mediated technologies to increase targeting, potency and persistence against hematologic malignancies and solid tumors.
"Throughout 2021, Gamida Cell made meaningful progress advancing our broad immunotherapy pipeline of potentially curative cell therapies for patients with solid tumor and blood cancers and other serious blood diseases, resulting in the recent initiation of our rolling BLA submission for omidubicel, which we expect to complete in the second quarter of this year. Additionally, we are continuing to work diligently to respond to the FDA regarding our IND for GDA-201, and expect to initiate our Phase 1/2 study in patients with follicular and diffuse large B-cell lymphomas once the clinical hold has been removed," said Julian Adams, Ph.D., chief executive officer of Gamida Cell. "Looking ahead in 2022, we are continuing to progress our genetically modified NK cell immunotherapy programs leveraging CAR- and CRISPR-mediated technologies focused on addressing unmet needs for patients with hematologic malignancies and solid tumors and we will select a product candidate for IND-enabling studies by the end of the year."

Fourth Quarter and Recent Developments

Omidubicel: Advanced Cell Therapy

BLA submission: Following the receipt of positive Type B meeting correspondence from the FDA confirming that analytical comparability has been established between Gamida Cell’s wholly-owned commercial manufacturing facility and the product that was manufactured for the Phase 3 study, Gamida Cell initiated a rolling BLA submission for omidubicel in the first quarter of 2022. As part of the rolling BLA, Gamida Cell submitted the nonclinical and clinical modules of the omidubicel BLA and is on-track to complete submission of all remaining modules of the BLA by the first half of 2022. In parallel with the BLA submission, the company is assessing alternatives for the commercialization of omidubicel, including potential U.S. or global partnerships.
New data presented at ASH (Free ASH Whitepaper): At the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021, Gamida Cell presented clinical updates and a health economic analysis on hospital resource utilization.
Data collected from a subset of patients in the omidubicel Phase 3 trial showed that, in addition to more rapid short-term hematopoietic recovery, omidubicel-treated patients had more rapid recovery of a wide variety of immune cells including CD4+ T cells, B cells, monocytes, NK cells, and dendritic cells than the control arm. The robust recovery of a broad range of the immune system correlated with and supported clinical data showing fewer severe bacterial, fungal, and viral infections in patients treated with omidubicel.
Resource utilization data during the first 100 days after transplant showed that omidubicel-treated patients had significantly shorter durations of hospitalization, intensive care unit time, consultant visits, procedures, and transfusions than the control arm. These data provide further evidence of the clinical benefit associated with the more rapid hematopoietic recovery in patients treated with omidubicel and the corresponding reduction in healthcare resource utilization.
An analysis of outcomes of patients with hematologic malignancies treated with omidubicel over a 10-year period showed long-term sustained bone marrow function and immune recovery, with a 10-year overall survival of 48%. These data provide further support for the long-term clinical benefit of omidubicel with long-lasting hematopoietic recovery.
GDA-201: NAM-Enabled NK Cell Therapy

IND for Phase 1/2 Study: Gamida Cell is working diligently to address the clinical hold on the IND for a Phase 1/2 study of GDA-201. Gamida Cell expects to initiate a company-sponsored Phase 1/2 clinical study in patients with follicular and diffuse large B-cell lymphomas in 2022.
New data presented at ASH (Free ASH Whitepaper): Gamida Cell presented 2-year survival and correlation data with cytokine IL7 at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021. This analysis provided longer follow-up in the investigator-led study of GDA-201 in patients with non-Hodgkin lymphoma and demonstrated an overall survival rate of 78% at two years with a median duration of response of 16 months.
NAM-Enabled NK Cell Pipeline Expansion

Advanced NAM-enabled genetically modified NK pipeline: Gamida Cell continues to progress its NAM-enabled genetically modified NK pipeline, which utilizes CAR, membrane bound- and CRISPR-mediated technologies to increase targeting, potency and persistence against hematologic malignancies and solid tumors. The company plans to execute preclinical proof of concept studies for these genetically modified NK therapeutic targets and to select a product candidate for IND enabling studies by the end of 2022. These therapeutic targets include:
GDA-301: Knockout of CISH (cytokine inducible SH2 containing protein) in NK cells using CRISPR/Cas9 in combination with a membrane-bound IL-15/IL-15Ra;
GDA-501: anti HER2 CAR-engineered NK cells to target solid tumors expressing HER2, based on a single-chain variable fragment of the widely used humanized monoclonal antibody trastuzumab; and
GDA-601: CRISPR Knockout of CD38 on NK cells combined with anti CD38 CAR. CD38 is an established immunotherapeutic target in multiple myeloma, but its expression on NK cells and its further induction during ex vivo NK cell expansion represents a barrier to the development of an anti CD38 CAR-NK cell therapy. Gamida Cell is advancing this program with a collaboration with the Dana-Farber Cancer Institute to study the in vitro cytotoxicity of GDA-601 in fresh samples from multiple myeloma patients.
GDA-401: A development candidate with the target still undisclosed.
Full Year 2021 Financial Results

Research and development expenses were $50.2 million in 2021, compared to $38.9 million in 2020. The increase was primarily due to a $5.4 million increase in omidubicel commercial manufacturing readiness activities and advancing the NK programs, as well as an increase of $5.9 million in broadening the company scientific capabilities and talent.
Commercial expenses in 2021 were $20.0 million, compared to $8.9 million in 2020. The increase was attributable mainly to a $6.5 million increase in commercial readiness expenses and a $4.6 million increase in headcount within the commercial organization. Going forward, the company anticipates reducing its near-term commercial readiness expenses, as it is assessing alternatives for the commercialization of omidubicel, including potential U.S. or global partnerships.
General and administrative expenses were $17.0 million in 2021, compared to $13.2 million in 2020. The increase was mainly due to a $2.6 million increase in professional services expenses and a $1.2 million increase in headcount and related expenses.
Finance expenses, net, were $2.6 million for 2021, compared to $0.6 million for 2020. The increase was primarily due to a $4.4 million interest expenses from convertible notes, offset by a $2.1 million capitalization and other non-cash expenses, and a $0.3 million increase in interest income from cash management.
Net loss for 2021 was $89.8 million, compared to a net loss of $61.6 million in 2020.
2022 Financial Guidance

Gamida Cell expects cash used for ongoing operating activities in 2022 to range from $60 million to $70 million.

Gamida Cell expects that its current cash and cash equivalents will support the company’s ongoing operating activities into mid 2023. This cash runaway guidance is based on the company’s current operational plans and excludes any additional funding and any business development activities that may be undertaken.

Expected Milestones in 2022

Omidubicel

Completion of full BLA submission to the FDA in the first half of 2022
GDA-201

Initiation of a company-sponsored Phase 1/2 clinical study in follicular and diffuse large B-cell lymphomas
NK cell pipeline expansion

Establish preclinical proof of concept studies of the NAM-enabled, genetically modified NK therapeutic targets
Select pipeline candidate for IND-enabling studies
Conference Call Information

Gamida Cell will host a conference call today, March 15, 2022, at 8:00 a.m. ET to discuss these financial results and company updates. A live webcast of the conference call can be accessed in the "Investors & Media" section of Gamida Cell’s website at www.gamida-cell.com. To participate in the live call, please dial 866-930-5560 (domestic) or 409-216-0605 (international) and refer to conference ID number 1696742. A recording of the webcast will be available approximately two hours after the event, for approximately 30 days.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the U.S. FDA and has also received Orphan Drug Designation in the U.S. and EU. Gamida Cell has completed an international, multi-center, randomized Phase 3 study (NCT0273029) evaluating the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing allogeneic bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant. That study achieved its primary endpoint, demonstrating a highly statistically significant reduction in time to neutrophil engraftment, a key milestone in a patient’s recovery from a stem cell transplant. The Phase 3 study also achieved its secondary endpoints of reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. Gamida Cell initiated a rolling BLA submission for omidubicel in the first quarter of 2022 with full BLA submission on track for first half of 2022. For more information about omidubicel, please visit View Source

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical trial results. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, GDA-201 improves antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. Gamida Cell expects to initiate a company-sponsored Phase 1/2 clinical study of GDA-201 in patients with follicular and diffuse large B-cell lymphomas in 2022. For more information about GDA-201, please visit View Source

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

On March 15, 2022 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of small protein therapeutics to address difficult-to-treat cancers, reported that management will participate in one-on-one meetings with investors at the SVB Leerink Biopharma Private Company Connect event, being held virtually March 29-31, 2022 (Press release, Sapience Therapeutics, MAR 15, 2022, View Source [SID1234610143]).

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On March 15, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has allowed an Investigational New Drug Application (IND) to proceed for its first genetically modified TIL therapy, IOV-4001, for the treatment of unresectable or metastatic melanoma and stage III or IV NSCLC (Press release, Iovance Biotherapeutics, MAR 15, 2022, View Source [SID1234610092]).

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IOV-4001 leverages the gene editing TALEN technology licensed from Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop potentially life-saving cell and gene therapies, to inactivate the gene coding for the PD-1 protein. By removal of this important barrier for T cells to attack cancer, IOV-4001 has the potential to become an optimized, next generation TIL therapy for several solid tumor cancers. A clinical study of IOV-4001 in patients with metastatic melanoma or stage III or IV NSCLC is expected to begin in 2022.

Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "IND allowance for IOV-4001 in two advanced cancers is an exciting milestone in the evolution of our TIL platform as we incorporate the gene editing TALEN technology to develop next generation TIL therapies. IOV-4001 provides a significant opportunity to deliver the combination of TIL and immune checkpoint inhibition within a single genome-edited TIL therapy in multiple solid tumor types. We look forward to bringing IOV-4001 into the clinic and to advancing additional next generation TIL therapies."

A poster highlighting preclinical activity, clinical-scale manufacturing process development, and characterization of IOV-4001 will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting. In the AACR (Free AACR Whitepaper) abstract, anti-tumor activity of IOV-4001 was superior to non-edited TIL, as well as non-edited TIL in combination with anti-PD-1, in a murine model.

About the TALEN Research Collaboration and Exclusive Worldwide Licensing Agreement

In January 2020, Iovance Biotherapeutics and Cellectis entered into a research collaboration and exclusive worldwide license agreement whereby Iovance licensed certain TALEN technology from Cellectis. The worldwide exclusive license enables Iovance to use certain TALEN technology addressing multiple gene targets to modify TIL for therapeutic use in several cancer indications. Iovance plans to initiate a clinical study of the first TALEN-edited TIL therapy, IOV-4001 (PD-1 inactivated TIL), in 2022. In addition, Iovance has a burgeoning preclinical pipeline of TALEN-edited TIL therapies, including double-knock out programs.

On March 15, 2022 GlaxoSmithKline (GSK) plc reported that it will present new findings in support of advancing treatment for certain gynaecologic cancers, including data evaluating Zejula (niraparib) and Jemperli (dostarlimab) at the upcoming Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (Press release, GlaxoSmithKline, MAR 15, 2022, View Source [SID1234610112]). The meeting will take place in Phoenix, Arizona, and virtually from 18-21 March 2022. The presentations demonstrate GSK’s commitment to improving outcomes for patients with gynaecologic cancers through research programmes that identify and address high unmet patient needs.

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Hesham Abdullah, Global Head of Oncology Development, GSK said: "The data we’re presenting at SGO will provide the research community with deeper insights about Zejula and Jemperli. We will also share data that furthers our understanding of ovarian and endometrial cancers, and real-world data that sheds light on potential gaps in the care of patients with gynaecologic cancer that need to be addressed."

Exploring optimal use of PARP inhibition maintenance therapy in ovarian cancer

Research being presented at SGO reinforces the role of first-line maintenance therapy with poly (ADP-ribose) polymerase (PARP) inhibitors in helping to optimise treatment outcomes for patients living with advanced ovarian cancer. This data contributes to the understanding of niraparib in the maintenance treatment of ovarian cancer.

Key oral presentations include:

OVARIO (oral presentation, ID #39): an oral plenary presentation featuring an updated analysis from this phase II study evaluating niraparib in combination with bevacizumab as first-line maintenance therapy in patients with ovarian cancer following platinum-based chemotherapy and bevacizumab.
ROYAL (oral presentation, ID #28): an oral plenary presentation featuring a real-world evidence study examining the evolution of the ovarian cancer treatment paradigm in the US and Europe from 2017 to 2020. The findings may help us better understand the treatment paradigm of ovarian cancer and identify remaining unmet needs.
In addition, Zai Lab (a GSK partner) will present a late-breaking oral presentation of the phase III PRIME study (late-breaking oral presentation, ID #5), featuring data evaluating niraparib (independently manufactured by Zai Lab) in Chinese patients with newly diagnosed advanced ovarian cancer using an individualized starting dose.

As part of GSK’s ongoing commitment to the ovarian cancer community, additional real-world studies assessing unmet needs will also be presented, including a study evaluating trends in first-line maintenance treatment use in patients with newly diagnosed advanced ovarian cancer, a study evaluating outcomes in patients with recurrent ovarian cancer who received niraparib as second-line maintenance therapy, and a study that assessed trends in niraparib starting dose as first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

Zejula is a once-daily oral monotherapy maintenance treatment approved for women with first-line platinum-responsive (complete or partial response) advanced ovarian cancer regardless of biomarker status in the US and the European Union (EU).

Advancing standard of care treatment in endometrial cancer

Key dostarlimab presentations at SGO include:

GARNET trial subgroup (poster presentation, ID #210): a post-hoc analysis from the GARNET trial evaluating the antitumour activity and safety of dostarlimab therapy in patients with endometrial cancer by age subgroups. This analysis will provide insights on outcomes in an older endometrial cancer patient population, potentially helping to inform treatment decisions.
Dostarlimab indirect treatment comparison (poster presentation, ID #216): an analysis comparing the clinical effectiveness of dostarlimab with doxorubicin in the treatment of advanced or recurrent endometrial cancer, which may help further contextualize how dostarlimab fits in the recurrent or advanced dMMR endometrial cancer treatment landscape.
The GARNET trial was the basis for the US and EU regulatory approvals of Jemperli, a programmed cell death receptor-1 (PD-1) blocking antibody.

Jemperli is the first anti-PD-1 monotherapy approved for endometrial cancer in the EU and received a conditional approval in April 2021 for the treatment of women with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum-containing regimen. The treatment also received accelerated approval based on tumour response rate and durability of response in the US for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, who have progressed on or following prior treatment with a platinum-containing regimen. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Full list of GSK’s presentations at SGO for niraparib and ovarian cancer:

Abstract Name

Presenter

Presentation Details

Evolution of the Ovarian Cancer Treatment Paradigm, Including Maintenance Treatment, in the US and Europe: A Real-World Chart Review Analysis (2017–2020)

K. Moore

Oral Presentation, ID #28

OVARIO, A Phase II Study of Niraparib + Bevacizumab in Advanced Ovarian Cancer Following Front-Line Platinum-Based Chemotherapy with Bevacizumab: Updated Analysis

M. Hardesty

Oral Presentation, ID #39

Poly (adenosine diphosphate [ADP]-ribose) Polymerase Inhibitor First-Line Maintenance Among Patients with Newly Diagnosed Advanced Ovarian Cancer in a Real-World Database

J. Liu

Poster Presentation, ID #351

Real-World Clinical Outcomes with Poly (adenosine diphosphate [ADP]-ribose) Polymerase Inhibitors as Second-Line Maintenance Therapy in Patients with Recurrent Ovarian Cancer in the United States

U. Matulonis

Poster Presentation, ID #353

Starting Dose of Niraparib as First-Line Maintenance Among Patients with Newly Diagnosed Advanced Ovarian Cancer in a Real-World Database

J. Liu

Poster Presentation, ID #352

Full list of GSK’s presentations at SGO for dostarlimab and endometrial cancer:

Abstract Name

Presenter

Presentation Details

Antitumor Activity and Safety of Dostarlimab Therapy in Patients with Endometrial Cancer by Age Subgroups: A Post-hoc Analysis from the GARNET Trial

A. Oaknin

Poster Presentation, ID #210

The Comparative Clinical Effectiveness of Dostarlimab Versus Doxorubicin in the Treatment of Advanced/Recurrent Endometrial Cancer

C. Mathews

Poster Presentation, ID #216

Patient Characteristics and Treatment Patterns in Patients With Advanced or Recurrent Endometrial Cancer in Europe: A Real-World Study

Q. Shen

Poster Presentation, ID #348

About ovarian cancer

Ovarian cancer is the 8th most common cancer in women worldwide.[1] Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence.[2] Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in the US and second most common gynaecologic cancer globally [3]. Approximately 15-20% of women with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis. [4]

Indications and Important US Safety Information for ZEJULA (niraparib)

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.
for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
a deleterious or suspected deleterious BRCA mutation, or
genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.

Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.
Important Safety Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated with ZEJULA monotherapy in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from 0.5 months to 4.9 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or pancytopenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports. Monitor all patients for signs and symptoms of PRES, which include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. Diagnosis requires confirmation by brain imaging. If suspected, promptly discontinue ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA is unknown.

Embryo-Fetal Toxicity and Lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women not to breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

Allergic reactions to FD&C Yellow No. 5 (tartrazine): ZEJULA capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%) and increased ALT (29%).

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis (20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

Treatment of Advanced HRD+ Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in QUADRA were nausea (67%), fatigue (56%), thrombocytopenia (52%), anemia (51%), vomiting (44%), constipation (36%), abdominal pain (34%), musculoskeletal pain (29%), decreased appetite (27%), dyspnea (22%), insomnia (21%), neutropenia (20%), headache (19%), diarrhea (17%), acute kidney injury (17%), urinary tract infection (15%), hypertension (14%), cough (13%), dizziness (11%), AST/ALT elevation (11%), blood alkaline phosphatase increased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).

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Indications and Important US Safety Information for JEMPERLI (dostarlimab-gxly)

JEMPERLI is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced:

endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen, or
solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on tumor response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI.
Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.
Immune-Mediated Pneumonitis

JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 1.4% (7/515) of patients, including Grade 2 (1.2%) and Grade 3 (0.2%) pneumonitis.
Immune-Mediated Colitis

Colitis occurred in 1.4% (7/515) of patients, including Grade 2 (0.8%) and Grade 3 (0.6%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies.
Immune-Mediated Hepatitis

JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.2% (1/515) of patients.
Immune-Mediated Endocrinopathies

Adrenal Insufficiency
Adrenal insufficiency occurred in 1.4% (7/515) of patients, including Grade 2 (0.8%) and Grade 3 (0.6%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Hypophysitis
JEMPERLI can cause immune-mediated hypophysitis. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Thyroid Disorders
Thyroiditis occurred in 0.4% (2/515) of patients; both were Grade 2. Hypothyroidism occurred in 7.2% (37/515) of patients, all of which were Grade 2. Hyperthyroidism occurred in 1.9% (10/515) of patients, including Grade 2 (1.7%) and Grade 3 (0.2%). Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis
JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
Immune-Mediated Nephritis with Renal Dysfunction

JEMPERLI can cause immune-mediated nephritis, which can be fatal. Nephritis occurred in 0.4% (2/515) of patients; both were Grade 2.
Immune-Mediated Dermatologic Adverse Reactions

JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity.
Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred in <1% of the 515 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy
Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur
Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis
Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica
Endocrine: Hypoparathyroidism
Other (Hematologic/Immune): Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection
Infusion-Related Reactions

Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/515) of patients receiving JEMPERLI. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction.
Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1–blocking antibody, which may occur despite intervening therapy. Monitor patients closely for transplant-related complications and intervene promptly.
Embryo-Fetal Toxicity and Lactation

Based on its mechanism of action, JEMPERLI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after their last dose. Because of the potential for serious adverse reactions from JEMPERLI in a breastfed child, advise women not to breastfeed during treatment with JEMPERLI and for 4 months after their last dose.
Common Adverse Reactions

The most common adverse reactions (≥20%) in patients with dMMR EC were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, decreased leukocytes, decreased albumin, increased creatinine, increased alkaline phosphatase, and increased alanine aminotransferase.

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GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.