On May 19, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that sixteen abstracts have been selected for virtual presentation, including one oral presentation, at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 4-8, 2021 (Press release, Karyopharm, MAY 19, 2021, View Source [SID1234580273]).

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Key abstracts to be presented at the meeting will feature clinical data for XPOVIO (selinexor), the Company’s first in class, oral Selective Inhibitor of Nuclear Export (SINE) compound, including: (i) multiple new subgroup analyses from the pivotal Phase 3 BOSTON study, including data results evaluating XPOVIO treatment for patients over the age of 65 years old and patients with RAS-mutated multiple myeloma; (ii) updated data from the Pomalyst (pomalidomide) and Kyprolis (carfilzomib) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; (iii) new results from a Phase 1 study evaluating the combination of XPOVIO and pembrolizumab in advanced RAS mutant and RAS wild type colorectal cancer; (iv) results from gene set enrichment analyses identifying molecular predictors of response to XPOVIO from the Phase 2/3 SEAL study in patients with dedifferentiated liposarcoma (DDLS); and (v) updated overall survival (OS) data from a Phase 1/2 study evaluating oral eltanexor, the Company’s second generation SINE compound, in patients with hypomethylating-agent refractory myelodysplastic syndrome (MDS).

"We are honored to be sharing this broad set of clinical data with the medical and scientific community this year at ASCO (Free ASCO Whitepaper), where we will be highlighting several important new datasets, including new subgroup analyses from both the BOSTON and STOMP studies in patients with relapsed or refractory multiple myeloma where we believe XPOVIO will become an important backbone therapy," said Sharon Shacham, PhD, MBA, Chief Scientific Officer of Karyopharm. "Additionally, we are pleased to see data from our growing pipeline of solid tumor studies, which will include new data from an ongoing combination study of XPOVIO and pembrolizumab in patients with advanced colorectal cancer as well as the discovery of certain molecular predictors of response to XPOVIO in patients with dedifferentiated liposarcoma, a difficult to treat cancer due to its resistance to chemotherapy and radiation. The data presented this year continue to demonstrate the broad clinical utility of XPO1 inhibition across a growing range of cancer types."

Select Abstracts Featuring XPOVIO (selinexor) in Multiple Myeloma

1. Title: Survival Among Older Patients with Previously Treated Multiple Myeloma Treated with Selinexor, Bortezomib, and Dexamethasone (XVd) in the BOSTON study

Presenter: Thierry Facon, University Hospital
Abstract #: 8019
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In an older patient population with a poor prognosis, XVd compared to Vd was associated with an OS benefit, improved progression-free survival (PFS) and an increased overall response rate (ORR) with reduced peripheral neuropathy and requires relatively short and infrequent clinic visits. XVd may be an effective regimen for patients 65 years of age or older. Adverse events (AEs) in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

2. Title: Effects of Weekly Selinexor, Bortezomib, Dexamethasone (XVd) Versus Standard Twice Weekly bortezomib and dexamethasone (Vd) on RAS-mutated previously treated multiple myeloma (MM)

Presenter: Christopher J. Walker, Karyopharm Therapeutics Inc.
Abstract #: 8027
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: Despite typically having the worst outcomes, patients with MM with any (K-, H- or N-) RAS mutation had a similar benefit from XVd as RAS wild-type MM, showing that the XVd combination can overcome therapy resistance characteristic of RAS-mutated MM. Mechanistically, selinexor induced down regulation of germinal center kinase and enhanced killing of RAS-mutated MM cells. With a manageable safety profile, the XVd regimen was able to overcome the therapeutic resistance of RAS-mutated multiple myeloma and improved PFS and OS in patients with RAS-mutated MM, and the data suggest that selinexor-containing regimens could be active in other RAS-mutant cancers. AEs in this study were generally consistent with other previously reported selinexor studies in MM.

3. Title: Effects of Refractory Status to Lenalidomide on Safety and Efficacy of Selinexor, Bortezomib, and Dexamethasone (XVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Previously Treated Multiple Myeloma

Presenter: Xavier Leleu, CHU de Poitiers, Hôpital La Mileterie
Abstract #: 8024
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In patients with previously treated multiple myeloma, PFS, ORR, and time to next treatment were significantly improved regardless of documented refractory status to any immunomodulatory drug (IMiD) or to lenalidomide specifically. These analyses support the use of the XVd combination for patients with disease refractory to lenalidomide and likely to any IMiD. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

4. Title: Oral Selinexor, Pomalidomide, and Dexamethasone (XPd) at Recommended Phase 2 Dose in Relapsed Refractory Multiple Myeloma (MM)

Presenter: Darrell White, QEII Health Sciences Center, Dalhousie University
Abstract #: 8018
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster Discussion Presentation
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: Once-weekly selinexor was shown in this Phase 1b/2 study to be safely combined with Pomalyst (pomalidomide) and low-dose dexamethasone (XPd) in patients with heavily pretreated MM. This all-oral XPd combination is highly active with an ORR of 65% at the recommended Phase 2 dose in 20 patients, compared to the expected ORR of ≤30% for the combination of Pomalyst and dexamethasone (Pd) or selinexor and dexamethasone, and has thus far produced durable responses with a median PFS of 12.2 months. The data suggest that the regimen was active even in patients with daratumumab-refractory MM. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

5. Title: Once Weekly Selinexor, Carfilzomib, and Dexamethasone (XKd) in Carfilzomib Nonrefractory Multiple Myeloma (MM) Patients

Presenter: Cristina Gasparetto, Duke University Cancer Center
Abstract #: 8038
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Highlights: In 27 patients with heavily pretreated MM (median of 4 lines of prior therapy), weekly XKd is highly active with an ORR of 78% and deep responses (≥VGPR 41%) with an overall PFS of 15 months; activity was strong even in patients with daratumumab refractory disease. AEs in this Phase 1/2b study were generally consistent with other previously reported selinexor studies in MM.

6. Title: Selinexor Containing Regimens in Patients with Multiple Myeloma (MM) Previously Treated with anti-CD38 Monoclonal Antibodies (aCD38 mAbs)

Presenter: Cristina Gasparetto, Duke University Cancer Center
Abstract #: e20020
Session type: Online abstract
Highlights: Selinexor-containing triplet combinations in 47 patients with MM previously treated with anti-CD38 mAb, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent anti-CD38 mAb-containing regimens in this retrospective analysis. Compared to historical controls who did not receive selinexor, median OS was much longer among these patients. The results show that selinexor-containing regimens maintain high levels of anti-MM activity, even in patients whose disease is refractory to daratumumab, immunomodulatory drugs and proteasome inhibitors. AEs in this study were generally consistent with other previously reported selinexor studies in multiple myeloma.

Select Abstracts Featuring XPOVIO (selinexor) in Solid Tumors

7. Title: Molecular Predictors of Response to Selinexor in Advanced Unresectable De-differentiated Liposarcoma (DDLS)

Presenter: Christopher J. Walker, Karyopharm Therapeutics Inc.
Abstract #: 11509
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Oral presentation
Session: Emerging Trends in Sarcoma Precision Medicine
Highlights: The randomized Phase 3 SEAL study of selinexor versus placebo in patients with heavily pretreated DDLS showed a significant improvement in PFS for selinexor. The molecular analyses reported here demonstrate that DDLS tumors responding to selinexor showed low expression of CALB1 and high GRM1. If validated, patients with DDLS whose tumors match this expression profile are especially likely to benefit from selinexor.

8. Title: Open-Label Phase 1 Study Evaluating the Tolerability and Anti-Tumor Activity of Selinexor and Pembrolizumab in Colorectal Cancer

Presenter: Talia Golan, Oncology Department Center Sheba Medical Center at Tel Hashomer
Session type: Online abstract
Abstract #: e15579
Highlights: Selinexor in combination with pembrolizumab has demonstrated disease control in patients with chemotherapy refractory, advanced/metastatic, microsatellite stable colorectal cancer (CRC). Greater anti-tumor activity was observed in patients with RAS mutations despite the absence of high microsatellite instability and/or deficient in mismatch repair. The therapy was well tolerated with no unanticipated adverse events observed.

9. Title: Selinexor in Combination with Weekly Paclitaxel in Patients with Advanced or Metastatic Solid Tumors: Results of an Open Label, Single-Center, Multi-arm Phase 1b Study

Presenter: Shannon Westin, The University of Texas MD Anderson Cancer Center
Abstract #: 5565
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Gynecologic Cancer
Highlights: Among 24 evaluable patients with heavily pretreated ovarian cancer, oral selinexor in combination with weekly paclitaxel resulted in an ORR of 17% and a clinical benefit rate (response + stable disease >12 weeks) of 58%. With prior taxane therapy, the ORR was 10% and with no prior taxane therapy, the ORR was 23%. The combination demonstrated promising clinical activity with manageable toxicity.

Abstracts Featuring Eltanexor in MDS

10. Title: Updated Overall Survival of Eltanexor for the Treatment of Patients with Hypomethylating Agent Refractory Myelodysplastic Syndrome

Presenter: Sangmin Lee, Weill Cornell Medical College
Abstract #: e19037
Session type: Online abstract
Highlights: Single-agent oral eltanexor was active in patients with high-risk, hypomethylating agent refractory MDS. Of the 20 enrolled patients, seven (35%) had marrow complete response (mCR), and five (25%) had stable disease (SD) for a total disease control (mCR+SD) rate of 60%. Of the 15 patients evaluable for efficacy, seven (47%) had mCR and five (33%) had SD. Patients who reached mCR (n=7) had significantly longer median OS than patients without mCR (n=8) or with progressive disease (n=3). Side effects were consistent with other studies of eltanexor without solid organ toxicity. Further evaluation of eltanexor in MDS as a single agent and in combination with other agents is ongoing.

Additional Abstracts to be Presented

11. Title: A Randomized, Open-label, Phase 3 Study of Low-dose Selinexor and Lenalidomide (Len) Versus Len Maintenance Post Autologous Stem Cell Transplant (ASCT) for Newly Diagnosed Multiple Myeloma (NDMM): ALLG MM23: Sealand

Presenter: Hang Quach, St. Vincent Hospital
Abstract #: TPS8055
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Hematologic Malignancies—Plasma Cell Dyscrasia

12. Title: U.S. Budget Impact (BI) Model for Selinexor, Bortezomib, and Dexamethasone (XVd) for the Treatment of Patients with Previously Treated Multiple Myeloma (MM)

Presenter: Mike Dolph, McGill University
Abstract #: e18839
Session type: Online abstract

13. Title: SIENDO/ENGOT-EN5/GOG-3055: A Randomized Phase 3 Trial of Maintenance Selinexor Versus Placebo After Combination Platinum-based Chemotherapy in Advanced or Recurrent Endometrial Cancer

Presenter: Ignace Vergote, BGOG and University Hospitals Leuven, Leuven Cancer Institute
Abstract #: TPS5610
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Gynecologic Cancer

14. Title: A Phase 1/2 Study of Selinexor in Combination with Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Presenter: Yazmin Odia, Miami Cancer Institute, Baptist Health South Florida (BHSF)
Abstract #: TPS2071
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Central Nervous System Tumors

15. Title: Digital Measurement of Functional Status of Patients with Glioblastoma

Presenter: Yasaman Demastani, Karyopharm Therapeutics Inc.
Abstract #: 2016
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Central Nervous System Tumors

16. Title: A Phase 1b/2 Study of Selinexor in Combination with Imatinib in Patients with Advanced Gastrointestinal
Stromal Tumor (GIST): SeliGIST/GEIS-41 Trial

Presenter: Cesar Serrano, West Virginia University School of Medicine Neurology & Neurosurgery
Abstract #: 11534
Date and time: Friday, June 4, 2021; 9:00 a.m. ET
Session type: Poster
Session: Sarcoma

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch.

About Eltanexor (KPT-8602)

Eltanexor (KPT-8602) is a second generation oral SINE compound, which is currently being investigated in clinical trials. Eltanexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. Eltanexor has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects.

On May 19, 2021 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported updated data from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA which will be presented as a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting (Press release, Advaxis, MAY 19, 2021, View Source [SID1234580272]). ADXS-503 is the first drug construct from the ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens.

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"These early results, which include a disease control rate of 44% in the first 9 evaluable patients treated with ADXS-503 as an add on therapy at progression with pembrolizumab, are particularly encouraging given the durable nature of disease control in 3 patients," said Suresh Ramalingam, M.D., Roberto C. Goizueta Chair for Cancer Research, Director, Division of Medical Oncology and Deputy Director of the Winship Cancer Institute at Emory University School of Medicine. "The translational results from the study provide interesting insights on the potential mechanism of action by which the addition of ADXS-503 may may be effective in this patient population."

Ken Berlin, Chief Executive Officer of Advaxis, said, "We are encouraged by these updated results which continue to support the potential of ADXS-503 to enhance and/or restore sensitivity to checkpoint inhibitors. The clinical activity observed to date in this challenging patient population, combined with a favorable safety profile, suggest that ADXS-503 may be an important new off-the-shelf immunotherapy treatment option. We look forward to continued progress in the clinic with our ADXS-HOT products which includes the ongoing Phase 1/2 study of ADXS-503 in NSCLC, and the expansion of the program to our planned Phase 1 Study of ADXS-504 for the treatment of early prostate cancer."

Key presentation highlights:

Highlights from the poster presentation titled, "A phase 1 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer (NSCLC) progressing on pembrolizumab as last therapy" presented by Missak Haigentz, M.D., Section Chief of Hematology and Oncology at Morristown Medical Center and Medical Director of Hematology and Oncology for Atlantic Health, and Study Investigator, include:

10 patients have been treated with ADXS-503 as an add on therapy to patients failing pembrolizumab as last therapy with 10 patients evaluable for safety and 9 patients evaluable for efficacy

Combination therapy was well tolerated with no DLTS or added toxicity of the two drugs. Grade 1 and 2, transient and reversible events included chills, fever, fatigue, in approximately half of the patients

The Disease Control Rate (DCR) was 44% (4/9)

Clinical benefit was durable, with an observed partial response (PR) and stable disease (SD) sustained for over a year, and another observed SD lasting over 6 months. An additional PR was maintained for approximately 4 months

Biomarker data demonstrate that patients who seem to achieve clinical benefit include those with PD-L1 expression ≥50%, secondary resistance disease to pembrolizumab and those who show proliferation and/or activation of NK and CD8+ T cells within the first weeks of therapy

Translational studies show:

Antitumoral T-cell responses elicited against hot-spot mutation antigens and/or tumor associated antigens (TAAs)

Emergence of naive CD8+ Tcell clones, suggesting reactivity against novel antigens

Induction of proliferation and/or activation of pre-existing CD8+ T-cell clones, including PD-1 upregulation

Enrollment in Part B of the ongoing study will continue to further evaluate the clinical benefit and immune effects of adding on ADXS-503 to patients progressing on pembrolizumab
The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. The two dose levels with monotherapy in Part A, (1 X108 and 5 X108 CFU) have been completed. Part B with ADXS-503 (1 X108 CFU) in combination with KEYTRUDA is currently enrolling its efficacy expansion for up to 18 patients at dose level 1 (1 X108 CFU + KEYTRUDA) with the potential to proceed to dose level 2 (5 X108 CFU + KEYTRUDA) at a later date. Part C, which is evaluating ADXS-503 in combination with KEYTRUDA (1 X108 CFU + KEYTRUDA) as a first line treatment for patients with NSCLC with PD-L1 expression ≥ 1% or who are unfit for chemotherapy is currently enrolling patients.

About ADXS-HOT
ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other proprietary cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. ADXS-HOT drug candidates are an off-the-shelf treatment, designed to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, DNA sequencing or diagnostic testing.

On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported results from a randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab (ERBITUX), an EGFR-targeted antibody, in patients who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab (pan-refractory) with metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, AVEO, MAY 19, 2021, View Source [SID1234580271]). Ficlatuzumab is AVEO’s potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The results will be presented by lead investigator Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Deputy Director, University of Arizona Cancer Center, at a poster discussion session of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 4-8 in a virtual setting.

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"Human papillomavirus (HPV) negative HNSCC is associated with poorer outcomes compared to HPV positive disease, particularly in pan-refractory disease, where there are currently no effective treatment options," said Professor Bauman. "Crosstalk between EGFR and HGF/cMet pathways is a known tumor intrinsic resistance mechanism, and HGF expression is known to be high in HPV negative disease, suggesting that the simultaneous inhibition of these pathways with cetuximab and ficlatuzumab could enhance anti-cancer response in this population. Results from this study are highly encouraging, with notable activity in pan-refractory, HPV negative disease warranting Phase 3 investigation."

"Results in patients with HPV negative disease who received ficlatuzumab and cetuximab produced prolonged progression free survival (PFS) and a response rate of 38%, which included two (18%) complete responses (CRs). These results suggest the combination has the potential to play a meaningful role in the treatment and the ultimate quality of life of patients with relapsed/metastatic HNSCC," said Michael Bailey, president and chief executive officer of AVEO. "The results compare favorably to historical controls of cetuximab in earlier lines of treatment. After receiving FDA feedback, we look forward to making a go/no-go decision by mid-year on the initiation of a Phase 3 study in an HPV negative HNSCC patient population, which we would expect to initiate in the first half of 2022, upon the availability of clinical drug supply."

In the Phase 2 study, a total of 60 patients with metastatic HNSCC who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab were randomized 1:1 to receive either ficlatuzumab alone (20 mg/kg IV) or ficlatuzumab in combination with cetuximab (500 mg/m2 IV) every two weeks. The ficlatuzumab/cetuximab combination arm met the study’s primary endpoint of median PFS, with the 32 evaluable patients in the arm demonstrating a median PFS of 3.6 months (lower bound 90% confidence interval [CI] 2.3 months; p=0.04), and 1.8 months (lower bound 90% CI: 1.7 months) for the 26 evaluable patients receiving ficlatuzumab alone. For the key secondary endpoint of overall response rate (ORR), the combination arm demonstrated an ORR of 19%, and 4% for ficlatuzumab alone.

Enrolled patients were stratified by HPV status, as HPV negative patients are known to have poorer outcomes. In an exploratory comparison of the HPV positive (n=16) and HPV negative (n=16) subgroups of the combination arm, HPV negative patients demonstrated both a superior ORR of 38% (versus 0% for HPV positive, p=0.02), with two CRs and four partial responses, and a median PFS of 4.1 months (versus 2.3 months for HPV positive, p=0.03). These results reflect updated data from those available at the time of abstract submission.

The combination of ficlatuzumab and cetuximab was generally well-tolerated with expected class toxicities from HGF/cMet inhibitors observed, including common adverse events of edema and hypoalbuminemia, and an uncommon adverse event of pneumonitis. Two treatment related deaths occurred, including pneumonitis (ficlatuzumab arm) and cardiopulmonary arrest (combination arm).

A copy of the poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

ASCO Presentation Details

Title: Randomized Phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).
Presenter: Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center
Abstract: 6015
Track: Head and Neck Cancer
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About Ficlatuzumab

Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) immunoglobulin G1 (IgG1) inhibitory antibody that binds to the HGF ligand with high affinity and specificity. HGF is the natural ligand of c-Met and blocking HGF inhibits signaling through the HGF/c-Met signaling pathway. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (HNSCC) and metastatic pancreatic ductal cancer (PDAC).

On May 19, 2021 Sanofi reported that Phase 1 data from the AMEERA-1 study evaluating amcenestrant, an investigational oral selective estrogen receptor degrader (SERD), will be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sanofi, MAY 19, 2021, View Source [SID1234580270]). In a pooled analysis, amcenestrant in combination with palbociclib showed encouraging antitumor activity in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC).

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"These early clinical data show that the combination of amcenestrant with palbociclib achieved encouraging antitumor activity," said Sarat Chandarlapaty, M.D., Ph.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center. "The analysis also demonstrated no clinically significant cardiac or ocular findings and an overall safety profile in line with what we saw in the monotherapy setting. It’s notable to see this kind of activity in patients with ER+ metastatic breast cancer, where there is a clear need for new therapeutic options."

In this preliminary analysis from the open-label AMEERA-1 study, amcenestrant was evaluated in dose escalation cohorts (Part C) at 200mg (n=9) and 400mg (n=6) daily and in a dose expansion cohort (Part D; n=30) at 200mg daily, all in combination with a standard dose of palbociclib. Eligible patients included post-menopausal women with ER+/HER2- MBC who were pre-treated with endocrine therapy in the advanced setting for at least six months or had resistance to adjuvant endocrine therapy.

In the pooled population exposed with amcenestrant at 200mg daily evaluable for response (n=35), the objective response rate (ORR) was 34% (90% CI: 21.1-49.6), with confirmed partial responses (PR) in 12/35 patients, and the clinical benefit rate (CBR) was 74% (90% CI: 59.4-85.9), with clinical benefit in 26/35 patients at 24 weeks. Amcenestrant 200mg daily in combination with palbociclib demonstrated a favorable overall safety profile (n=39), with treatment related adverse events (TRAEs) attributable to amcenestrant similar to those observed with monotherapy. For all grade events, amcenestrant TRAEs occurred in 72% and to palbociclib in 90% of patients, and for grade ≥3 in 15% and 46% of patients, respectively. The most frequent non-hematological amcenestrant TRAEs included fatigue (18%) and nausea (18%), all grade ≤2. No clinically significant cardiac or ocular safety findings occurred.

"The Phase 3 AMEERA-5 study was built upon promising preclinical and clinical data, including the data presented here at ASCO (Free ASCO Whitepaper), and expands our knowledge of amcenestrant as a potential best-in-class oral endocrine backbone therapy for ER+/HER2- breast cancer," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "A significant need exists for more treatment options for ER+ breast cancer, the most common type of breast cancer, accounting for approximately 75% of all breast cancers diagnosed today."

Amcenestrant is an oral SERD that antagonizes and degrades the estrogen receptor (ER) resulting in inhibition of the ER signaling pathway. Amcenestrant is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

Amcenestrant clinical development program

The comprehensive development program for amcenestrant has been designed to evaluate its role: (1) as a single agent in second-line or later lines of treatment of ER+/HER2- MBC, (2) in combination with palbociclib in the first-line treatment of ER+/HER2- MBC, and (3) to explore its potential in early-stage breast cancer patients in the adjuvant setting. Late last year, the Phase 3 AMEERA-5 clinical trial investigating amcenestrant in combination with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, as a first-line therapy for patients with ER+ MBC, was initiated.

A pivotal study (AMEERA-3) of amcenestrant versus physician’s choice in locally advanced or metastatic ER+ breast cancer is fully recruited. The pivotal readout is now expected in H2 2021. Of note, the trial recently passed a Data Safety Monitoring Committee (DSMC) futility analysis.

About ER+ metastatic breast cancer

MBC is breast cancer that has spread outside the mammary gland to another part of the body, such as the liver, brain, bones or lungs. It is also known as Stage IV and is the most advanced stage of breast cancer.1 About two of every three cases of breast cancer are HR+, meaning the cancer is fueled by the hormones estrogen or progesterone.2 HR+ breast cancers can be classified as ER+ and/or progesterone receptor-positive (PR+).2 ER+ breast cancer accounts for approximately 75% of all breast cancers3 and is the most common type of breast cancer diagnosed today.4 The five-year relative survival for distant (cancer that has metastasized) female breast cancer is 28.1%.5 Endocrine therapies were among the first treatments to be administered for HR+ MBC and are considered standard of care in the first-line setting. However, new options are needed as resistance often emerges, limiting the effectiveness of these treatments for patients with metastatic disease over time.6

About the AMEERA-1 clinical trial

AMEERA-1 is an open-label, Phase 1/2, first-in-human study designed to evaluate amcenestrant as a monotherapy and in combination with targeted therapies in postmenopausal women with ER+/HER2- MBC. Parts A (dose escalation) and B (dose expansion) were designed to determine the maximum tolerated dose of amcenestrant administered as monotherapy, while Parts C and D are evaluating dose escalation and expansion for amcenestrant in combination with palbociclib to determine the recommended Phase 2 dose for the combination and to characterize its safety profile. Primary efficacy objectives include antitumor activity by ORR and CBR per RECIST v1.1 criteria, as well as characterizing the overall safety profile of amcenestrant as a monotherapy and in combination with palbociclib. Eligible patients included women with histological diagnosis of breast adenocarcinoma with locally advanced or metastatic ER+/HER2- disease and at least six months of prior exposure to endocrine therapy, including patients with early relapse while on adjuvant endocrine therapy that was initiated more than 24 months ago, or who relapsed less than 12 months after completion of adjuvant endocrine therapy.7

Dr. Chandarlapaty has provided consulting services to Sanofi.

On May 19, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company that utilizes the latest biotechnology to discover and deliver novel medicines, reported new data for zandelisib, an investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor in clinical development for the treatment of B-cell malignancies (Press release, MEI Pharma, MAY 19, 2021, View Source [SID1234580269]). The research and the design of a Phase 3 study will be presented in three posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 being held virtually June 4-8, 2021.

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"We are encouraged by the zandelisib data being shared at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, specifically the data that showed zandelisib activity across differing patient groups, including POD24 – a group that typically has a poor prognosis and would generally be expected to meet the inclusion criteria of our Phase 3 COASTAL study. Additionally, the data reporting on the combination of zandelisib and zanubrutinib, demonstrated the potential to induce robust and durable responses against various B-cell malignancies with a combination that is generally well-tolerated," said Richard Ghalie, M.D., chief medical officer at MEI Pharma. "With topline data from the Phase 2 TIDAL study on track to be reported by the end of this year, we remain committed, in collaboration with our global partner Kyowa Kirin, to the zandelisib development program and its potential to deliver a best-in-class treatment option to patients with B-cell malignancies as a monotherapy or in combination with other therapies."

The presentations will present updated data from a Phase 1b study of zandelisib + – rituximab that show the compound continues to be generally well tolerated with an 82% overall response rate in patients with relapsed or refractory (r/r) follicular lymphoma (FL) who had progression of disease within 24 months of first line chemoimmunotherapy (POD24). An overall response rate of 93% was observed in patients with r/r FL and were non-POD24. POD24 status is a robust predictor of reduced overall survival in FL patients. The response rate in all 37 r/r FL patients was 87%.

Additionally, the presentations will include new data from the Phase 1b trial exploring zandelisib in combination with zanubrutinib (marketed as BRUKINSA), an inhibitor of Bruton’s tyrosine kinase ("BTK") developed by BeiGene, Ltd. ("BeiGene"), in patients with (r r) B-cell malignancies. In this study, the combination of zandelisib and zanubrutinib was generally well tolerated in the 20 patients enrolled in the safety evaluation cohort. The combination administered on an optimized dosing regimen did not result in additive toxicity to each agent alone. Further, 100% of patients (n=16) with r/r indolent B-cell malignancies and chronic lymphocytic leukemia (CLL) achieved an objective response.

The trial design for the Phase 3 COASTAL study evaluating zandelisib in combination with rituximab in patients with r r indolent non-Hodgkin’s lymphoma (iNHL), will also be highlighted in a poster presentation. The COASTAL study is intended to act as the required confirmatory study for the potential U.S. accelerated approval of zandelisib in patients with r/r FL or marginal zone lymphoma (MZL) who have received one or more prior lines of treatment and is also intended to support FDA approval for additional indications and regulatory marketing applications globally.

"Data from the early Phase 1 trials indicate that zandelisib displays high selectivity for the phosphatidylinositol 3-kinase delta (PI3K) isoform as well as durability, with PI3K playing a key role in the proliferation and survival of hematologic cancers," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "Zandelisib has distinct pharmaceutical properties and we look forward to continuing the development of the compound, in partnership with MEI Pharma, with the hope that more data will add to the understanding of zandelisib and potentially yield another option for patients with B-cell malignancies."

Details on the three posters are included below.

Updated Clinical Data from the Phase 1b Study Evaluating Zandelisib in Patients with Relapsed or Refractory Follicular Lymphoma

Poster title: Efficacy and Safety of the PI3Kδ Inhibitor Zandelisib (ME-401) on an Intermittent Schedule (IS) in Patients with Relapsed Refractory Follicular Lymphoma (FL) with Progression of Disease within 24 Months of First-Line Chemoimmunotherapy (POD24)
Available for on-demand viewing online: Beginning on June 4, 2021 at 6:00 a.m. PT here
Poster will also be available for download via the MEI Pharma website
John Pagel, M.D., Ph.D., lead author on the poster, study investigator, and Chief of Hematologic Malignancies, Swedish Cancer Center, commented: "The group of relapsed or refractory follicular lymphoma patients that experience progression of disease within 24 months of first line chemoimmunotherapy have a poorer long-term prognosis compared to the patients with follicular lymphoma who relapse later than 24 months and represent an area of high need for new treatment options. The positive results reported today indicate the potential for zandelisib to provide a new treatment option for high-risk patients with relapsed or refractory follicular lymphoma."

Study Details:
The ongoing Phase 1b clinical study is a multi-arm, open-label, dose optimization trial evaluating zandelisib as a monotherapy and in combination with other therapies in patients with r r B-cell malignancies. The data reported today is for patients receiving zandelisib administered on the intermittent schedule: once daily at 60 mg for two 28-day cycles and then on an intermittent schedule of once daily dosing for the first 7 days of each subsequent 28-day cycle (i.e. the intermittent schedule or IS). A total of 37 r/r FL patients have been treated with zandelisib on the intermittent schedule, as a monotherapy or in combination with rituximab. Of the 37 r/r FL patients, 22 were POD24. POD24 is a robust predictor in FL of reduced overall survival.

The overall response rate in 37 patients with r r FL was 87% with 27% achieving a complete response. The overall response rate in POD24 patients was 82% and 93% in non-POD24 patients. The complete response rate in POD24 patients was 18% and 40% in non-POD24 patients.

Overall Response Rate

All

(N = 37)

POD24

(n = 22)

Non-POD24

(n = 15)

ORR, n (%)*

32 (87)

18 (82)

14 (93)

Monotherapy, n N (%)

Combination with rituximab, n N (%)

14 18 (78)

18 19 (95)

8 11 (73)

10 11 (91)

6 7 (86)

8 8 (100)

Prior lines of therapy, n N (%)

1 line of prior therapy

≥ 2 lines of prior therapy

14 16 (88)

18 21 (86)

5 7 (71)

13 15 (87)

9 9 (100)

5 6 (83)

CR rate, n (%)

10 (27)

4 (18)

6 (40)

* Imaging scans were obtained after 2 and 6 cycles, and then every 6 cycles. Response was reported based on Lugano criteria.

Duration of Response
Median duration of response in POD24 and non-POD24 patients has not yet been reached. Median duration follow-up is 15.8 months (range: 5.6-33.1) in POD24 patients and 17 months (range: 1.2-28.6) in non-POD24.

Follow-up = Time from first response to treatment discontinuation date or data cutoff of 10DEC2020 for ongoing patients

Follow-up = Time from first response to treatment discontinuation date or data cutoff of 10DEC2020 for ongoing patients

Progression Free Survival
Progression free survival in POD24 patients is 12.5 months and in the non-POD24 group the median is not yet reached. Median follow-up time in the POD24 and non-POD24 groups is 19.4 (range 1.8-36.5) and 18.2 (range: 3.0-30.4) months, respectively.

Follow-up = Time from first day on study to treatment discontinuation or data cutoff of 10DEC2020

Follow-up = Time from first day on study to treatment discontinuation or data cutoff of 10DEC2020

Adverse Events
Zandelisib was generally well-tolerated. No difference in adverse events was observed between POD24 and non-POD24 groups. The discontinuation rate due to any treatment emergent adverse event was 8% (n=3), and the incidence of Grade ≥ 3 TEAE was as follows:

Grade ≥3 Adverse Events in ≥2 Patients

N = 37

N (%)

Neutropenia

6 (16)

ALT AST increased

3 (8)

Rash

3 (8)

Diarrhea

2 (5)

Colitis

2 (5)

Hypokalemia

2 (5)

Hyponatremia

2 (5)

Coronavirus infection

2 (5)

Phase 1b Study Evaluating Zandelisib in Combination with Zanubrutinib in Patients with B-cell Malignancies

Poster title: Initial Results of the Combination of PI3Kδ Inhibitor Zandelisib (ME-401) and the BTK Inhibitor Zanubrutinib in Patients (pts) with r r B-cell Malignancies
Available for on-demand viewing online: Beginning on June 4, 2021 at 6:00 a.m. PT here.
Poster will also be available for download via the MEI Pharma website
Jacob Soumerai, M.D., lead author on the poster, study investigator and Assistant Professor at Harvard Medical School and Massachusetts General Hospital Cancer Center, commented: "The data reported today for zandelisib in combination with zanubrutinib are encouraging, both in terms of preliminary safety and efficacy, and support the expansion of the evaluation of this orally administered combination in various B-cell malignancies."

Study Details
The ongoing Phase 1b clinical study is a multi-arm, open-label, dose optimization trial evaluating zandelisib as a monotherapy and in combination with other therapies in patients with r r B-cell malignancies. The data reported today is for 20 patients receiving zandelisib in combination with zanubrutinib. Two treatment dosing regimens were explored: Group A received zandelisib 60 mg, oral, daily continuously for 8 weeks followed by days 1-7 of each subsequent 28-day cycle, and zanubrutinib (marketed as BRUKINSA by BeiGene, Ltd.), 160 mg oral, twice daily; Group B received zandelisib 60 mg, oral, daily on days 1-7 of each 28-day cycle starting Cycle 1 and zanubrutinib 80 mg, oral, twice daily. Group A enrolled a total of 7 patients: 1 FL, 3 CLL, 1 MZL, 1 mantle cell lymphoma (MCL), and 1 diffuse large B-cell lymphoma/high grade B-cell lymphoma (DLBCL/HGBCL). Group B enrolled a total of 13 patients: 7 FL, 2 CLL, 1 MZL, and 3 DLBCL HGBCL. Treatment was continued until disease progression, intolerance or withdrawal of consent.

Overall Response Rates
The overall response rate in all evaluable patients with r r indolent B-cell malignancies and CLL was 100%. No response was noted in the 2 patients with DLBCL/HGBCL. Responses were durable with median follow up of 6.6 months (0.6-21.3) with the majority of responders still on treatment.

Evaluable

n = 18

FL
(n = 8)

CLL SLL
(n = 5)

MZL
(n = 2)

MCL
(n = 1)

DLBCL HGBCL
(n = 2)

ORR*, n (%)

8 (100)

5 (100)

2 (100)

1 (100)

0

Group A

1 (100)

3 (100)

1 (100)

1 (100)

0

Group B

7 (100)

2 (100)

1 (100)

0

0

*CR CRi in 2/8 FL (25%) and 2/5 CLL (40%). Imaging scans at month 3, 7, 13, and then every 6 months until progression. Response reported based on Lugano criteria and iwCLL. 2/20 patients (1 DLBCL, 1 HGBCL) did not have on-therapy scans: 1 had clinical PD and 1 had AE due to prior therapy and discontinued early. Median follow-up time was 6.6 months for all patients (range 0.6-21.3), 3.6 months for Group A (range 0.6-21.3), and 6.6 months for Group B (range 1.9-14.1).

Treatment Emergent Adverse Events
The combination of zandelisib 60 mg oral, daily on days 1-7 of each 28-day cycle starting Cycle 1 and zanubrutinib 80 mg, oral, twice daily was well tolerated across the various B-cell malignancies in the completed part of the study. The combination administered on the optimized, Group B, dosing regimen did not result in additive toxicity to each agent alone. One of the two patients with Grade 3 AST ALT increases in Group B was successfully retreated and continued therapy.

Group A

(n = 7)

Group B

(n = 13)

Adverse Event, n (%)

All Grades

Grade ≥ 3

All Grades

Grade ≥ 3

Neutropenia

4 (57)

*3 (43)

6 (46)

3 (23)

ALT increased

2 (29)

2 (29)

2 (15)

**2 (15)

AST increased

2 (29)

2 (29)

3 (23)

**2 (15)

Anemia

1 (14)

*1 (14)

2 (15)

1 (8)

Hyperkalemia

2 (29)

0

2 (15)

1 (8)

Thrombocytopenia

4 (57)

*2 (29)

3 (23)

1 (8)

Pleural Effusion

2 (29)

*1 (14)

0

0

Rash

1 (14)

1 (14)

2 (15)

0

Appendicitis

0

0

1 (8)

1 (8)

Ascites

1 (14)

*1 (14)

0

0

CMV colitis

1 (14)

1 (14)

0

0

Fatigue

4 (57)

1 (14)

2 (15)

0

Pneumonia

2 (29)

*1 (14)

0

0

Tumor lysis syndrome

0

0

1 (8)

1 (8)

Diarrhea

3 (43)

0

3 (23)

0

Atrial fibrillation

1 (14)

0

0

0

* Group A: 1 DLBCL patient experienced Grade 3 AE on Day 0 attributed to prior therapy and discontinued treatment on Day 17, then progressed on Day 23 and died with Grade 4 thrombocytopenia and pleural effusion, Grade 3 pneumonia, anemia, and ascites. ** Group B: DLT.

This Phase 1b study is continuing to enroll expansion cohorts in r r FL and MCL to further evaluate the combination of zandelisib 60 mg administered on days 1-7 starting Cycle 1 and zanubrutinib administered at 80 mg bid.

COASTAL Phase 3 Study Design

Poster title: Coastal: A phase 3 study of the PI3Kδ inhibitor zandelisib with rituximab (R) versus immunochemotherapy in patients with relapsed indolent non-Hodgkin’s lymphoma (iNHL)
Available for on-demand viewing online: Beginning on June 4, 2021 at 6:00 a.m. PT here.
Poster will also be available for download via the MEI Pharma website
The global, randomized, two-arm Phase 3 study will compare zandelisib plus rituximab to standard of care chemotherapy plus rituximab, is expected to enroll 534 patients, and the primary efficacy endpoint is progression-free survival. Zandelisib will be administered once daily for two 28-day cycles followed by an intermittent schedule of once daily dosing for one week of each subsequent 28-day cycle.

"As a potent, highly selective inhibitor of the PI3Kδ isoform, zandelisib has a differentiated therapeutic profile that makes it an ideal candidate to evaluate in different B-cell malignancies, both as a monotherapy and combined with other agents" said Professor Wojciech Jurczak, M.D., Ph.D., COASTAL principal investigator, Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology in Kraków, Poland. "The initiation of the COASTAL study will be an important milestone as we evaluate zandelisib’s potential as a best-in-class PI3Kδ therapy, optimized by a unique dosing schedule."

Clinical study of zandelisib as a monotherapy or in combination with other agents support its clinical development for B-cell malignancies. In clinical studies, zandelisib administered as a 2-month induction followed by intermittent schedule maintenance dosing achieved an 83-89% response rate, with median duration of response not reached in r r follicular and marginal zone lymphomas when given as a monotherapy or in combination with rituximab. Durable responses have been reached in patients treated with zandelisib as either a monotherapy or in combination, regardless of prior therapies or tumor bulk. Utilizing an optimized dosing schedule of zandelisib, there has been less than 10% of Grade 3 or higher immune-mediated adverse events of special interest associated with PI3Kδ inhibitors in patients with B-cell malignancies. Zandelisib is currently in the Phase 2 TIDAL study as a monotherapy for patients with r/r follicular or marginal zone lymphoma. The COASTAL study enrollment is expected to be initiated around mid-2021.

About Zandelisib
Zandelisib (formerly called ME-401), a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, treatment for patients with B-cell malignancies. In March 2020 the U.S. FDA granted zandelisib Fast Track designation for treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies.

In April 2020, MEI and Kyowa Kirin Co., Ltd. (Kyowa Kirin) entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin are co-developing and co-promoting zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S.

Ongoing clinical studies of zandelisib include TIDAL (Trials of PI3K DeltA in Non-Hodgkin’s Lymphoma), a global Phase 2 study evaluating zandelisib as a monotherapy across two study arms: the first study arm for the treatment of adults with relapsed and refractory follicular lymphoma and the second study arm for marginal zone lymphomas, in both cases after failure of at least two prior systemic therapies including chemotherapy and an anti-CD20 antibody. The primary endpoint of the study is the objective response rate. Subject to the results and discussions with FDA, data from each study arm are intended to be submitted to FDA to support separate accelerated approval marketing applications under 21 CFR Part 314.500, Subpart H.

Also ongoing is a Phase 2 pivotal study in Japan in patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin.

About PI3K Delta
Phosphatidylinositol 3-kinase delta ("PI3Kδ") is often overexpressed in cancer cells and plays a key role in the proliferation and survival of hematologic cancers. Zandelisib displays high selectivity for the PI3K delta isoform and has distinct pharmaceutical properties from other PI3K delta inhibitors.

About Follicular Lymphoma
Follicular lymphoma (FL) is the most common indolent lymphoma, comprising about 20-30% of all non-Hodgkin lymphomas (NHL). The disease also forms on B cells, is chronic in most cases and tends to progress slowly. Most people diagnosed with FL are over 65 years of age. Sometimes follicular lymphomas can change into diffuse large B-cell lymphoma, a fast-growing (aggressive) type of NHL.