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 Allarity Therapeutics A/S ("Allarity" or the "Company") reported that its Board of Directors has resolved to carry out a share issue with preferential rights for the Company’s existing shareholders, including warrants (the "Offering"), supported by an authorization granted to the Board of Directors at an Extraordinary General Meeting on 15 April 2021 (Press release, Allarity Therapeutics, MAY 19, 2021, View Source [SID1234580289]). Allarity is also today publishing a prospectus (the "Prospectus"), which has been prepared in connection with the Offering, for up to a maximum of 120,891,157 offer units. Each unit ("Offer Unit") consists of one (1) new share of nominal DKK 0.05 ("New Share") with one (1) warrant attached which confers the right to subscribe one (1) share of nominal DKK 0.05 share in the Company at an exercise price of SEK 1.7 ("Investor Warrant"). New Shares are subscribed against cash payment of SEK 0.85. Investor Warrants are subscribed without payment. Guarantees and undertakings of in excess of SEK 100 million from underwriters and guarantors have been received.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The subscription period starts on 25 May 2021 and ends on 8 June 2021. The Company will receive SEK 102.8 million upon full subscription of the Offer Units, before transaction costs. The Investor Warrants have a term of 22 months and the Company expects to receive additional net proceeds of approximately SEK 206 million upon full subscription and full exercise of the Investor Warrants. The rights issue is also open to the public to the extent it is not fully subscribed for by existing shareholders.

Expected timetable of principal events:

18 May 2021: Last day of trading in the share, including the right to receive subscription rights.
19 May 2021: Publication of the EU growth prospectus.
19 May 2021: First day of trading in the share, excluding the right to receive subscription rights.
20 May 2021: Record date for participation in the Offering, i.e. holders of shares who are registered in the share register maintained by Euroclear Sweden AB on this date will receive subscription rights for participation in the Offering with preferential right.
25 May – 3 June 2021: Trading in subscription rights.
25 May – 8 June 2021: Subscription period.
25 May – until registration is completed with the Danish Business Authority: Trading in BTUs (paid subscription units).
10 June 2021: Expected day for publication of the outcome of the Offering
Allarity’s CEO, Steve Carchedi, stated, "Allarity remains focused on delivering clinical and commercial progress on our three high-priority projects, dovitinib, stenoparib and IXEMPRA. The potential value inflection points for all of these projects could appear on the horizon as soon as within a year or two. This situation presents the circumstances for our Company to offer a compelling investment opportunity to both existing and new shareholders, through the publication of the Prospectus describing the Offering."

Investors in the Offering will have the possibility to exercise their Investor Warrants in five two-week windows during the 22-month term, following the completion of the Offering, during which the Investor Warrants can be exercised. The windows will occur in October 2021, March 2022, August 2022, November 2022, and April 2023.

The Prospectus is available via the Company’s website (www.allarity.com).

Advisors

Aalto Capital AB is the sole global coordinator and bookrunner in connection with the Offering and Hagberg & Aneborn Fondkommission AB the issuing agent. Mazanti-Andersen Advokatpartnerselskab is legal advisor to the Company.

About the Drug Response Predictor – DRP Companion Diagnostic
Allarity uses its drug specific DRP to select those patients who, by the genetic signature of their cancer, are found to have a high likelihood of responding to the specific drug. By screening patients before treatment, the response rate can be significantly increased. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including genomic information from cell lines combined with clinical tumor biology and prior clinical trial outcomes. DRP is based on messenger RNA from the patient’s biopsies. DRP has proven its ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients in nearly 40 clinical studies that were examined, including an ongoing, prospective Phase 2 trial. The DRP platform can be used in all cancer types and is patented for more than 70 anti-cancer drugs.

On May 19, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company, reported that 16 abstracts representing the breadth of the Gilead-Kite Oncology portfolio will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 4-8, 2021 (Press release, Gilead Sciences, MAY 19, 2021, View Source [SID1234580305]). The abstracts, including two oral presentations, expand on the clinical profiles of Gilead’s antibody-drug conjugate (ADC), as well as Kite’s chimeric antigen receptor (CAR) T-cell therapies across a range of cancers, including in existing indications and for investigational uses.

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"Gilead-Kite Oncology is rapidly advancing transformative science for people facing historically difficult-to-treat cancers," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Our first-in-class, TROP-2 directed ADC therapy is already having a meaningful impact for people with metastatic triple-negative breast and urothelial cancers, and data at ASCO (Free ASCO Whitepaper) will add further insight into its utility in TNBC in both monotherapy and future combination treatment approaches."

"CAR T-cell therapy has changed the lives of patients suffering from certain forms of non-Hodgkin lymphoma, and our data at ASCO (Free ASCO Whitepaper) demonstrate important progress in extending the benefits to more patients in need," said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. "As we aim to bring CAR T to people with many different hematologic malignancies, we are just beginning to scratch the surface of what is possible."

A list of accepted abstracts follows here:

Abstract Disposition

Abstract Title

Gilead Presentations

Oral #1011

6:00 am PT/9:00 am ET

Outcomes in Patients Aged ≥65 Years in the Phase 3 ASCENT Study of Sacituzumab Govitecan (SG) in Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #1077

Assessment of Sacituzumab Govitecan (SG) versus Treatment of Physician’s Choice (TPC) Cohort by Agent in the Phase 3 ASCENT Study of Patients with Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #1080

Assessment of Sacituzumab Govitecan (SG) in Patients with Prior Neoadjuvant/Adjuvant Chemotherapy in the Phase 3 ASCENT Study in Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #TPS602

Phase 3 Postneoadjuvant Study Evaluating Sacituzumab Govitecan, an Antibody Drug Conjugate in Primary HER2-Negative Breast Cancer Patients with High Relapse Risk After Standard Neoadjuvant Treatment – SASCIA

Poster #TPS1102

Saci-IO HR+: Randomized Phase 2 Trial of Sacituzumab Govitecan (SG) +/- Pembrolizumab in PD-L1+ Hormone Receptor-Positive (HR+) / HER2- Metastatic Breast Cancer (MBC)

Poster #TPS1106

Saci-IO TNBC: Randomized Phase 2 Trial of Sacituzumab Govitecan (SG) +/- Pembrolizumab in PD-L1– Metastatic Triple-Negative Breast Cancer (mTNBC)

Poster #TPS7055

Magrolimab + Azacitidine versus Azacitidine + Placebo in Untreated Higher Risk Myelodysplastic Syndrome (MDS): The Phase 3, Randomized, ENHANCE Study

Poster #2559

GS-3583, a Novel FLT3 Agonist Fc Fusion Protein, to Expand Conventional Dendritic Cells in Healthy Volunteers

Poster #TPS3147

Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS-3583, a FLT3 Agonist Fc Fusion Protein, in Patients with Advanced Solid Tumors

Kite Presentations

Oral #7002

11:30 am PT/2:30 pm ET

Phase 2 Results of the ZUMA-3 Study Evaluating KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL)

Poster #7515

Outcomes in ZUMA-5 with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL) Who Had the High-Risk Feature of Progression within 24 Months from Initiation of First Anti-CD20–Containing Chemoimmunotherapy (POD24)

Poster #7536

Favorable Tumor Immune Microenvironment (TME) and Robust Chimeric Antigen Receptor (CAR) T-Cell Expansion May Overcome Tumor Burden and Promote Durable Efficacy with Axicabtagene Ciloleucel (Axi-Cel) in Large B Cell Lymphoma (LBCL)

Poster #7547

Outcomes with KTE-X19 in Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL) in ZUMA-2 Who Had Progression of Disease within 24 Months of Diagnosis (POD24)

Poster #7548

Updated Outcomes with Axicabtagene Ciloleucel (Axi-Cel) Retreatment in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL) in ZUMA-5

Poster #7552

Real-World Evidence of Axicabtagene Ciloleucel (Axi-Cel) for the Treatment of Large B-Cell Lymphoma (LBCL) in the United States

Poster #e19548

Online Publication Only

Clinical Outcomes in Patients Relapsed/Refractory After ≥ 2 Prior Lines of Therapy for Follicular Lymphoma: A Systematic Literature Review and Meta-Analysis

All poster presentations will be made available on-demand beginning Friday, June 4 at 6:00 am PT/9:00 am ET.

For more information, including a complete list of abstract titles at the meeting, please visit: View Source

On May 19, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that an abstract reporting on the first-in-human study of the Bcl-2 inhibitor, lisaftoclax (APG-2575), in patients with relapsed/refractory chronic lymphocytic lymphoma/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies has been published in the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting’s official website (Press release, Ascentage Pharma, MAY 19, 2021, View Source;ascentage-pharma-to-announce-updated-data-of-lisaftoclax-apg-2575-demonstrating-an-orr-of-around-80-and-therapeutic-potential-in-patients-with-rr-cllsll-in-oral-presentation-301295527.html [SID1234580321]). Results from this global Phase I study demonstrated an ORR of 85.7%, and favorable tolerability and safety profiles in patients with R/R CLL /SLL.

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The updated results from this study will be released in an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting convening on June 4 to 8, 2021. This year, abstracts reporting on four clinical studies of the Ascentage Pharma’s three apoptosis-target drug candidates have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting, and two have been selected for oral presentations.

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

"As a Bcl-2 inhibitor that has demonstrated efficacy, lisaftoclax is the second in the world and the first in China. These data of lisaftoclax suggest the potential for a safe, efficacious, and ‘patient-friendly’ treatment alternative for patients with R/R CLL and other hematologic malignancies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moreover, these results which will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting are a testament to our progress in advancing the research and development of apoptosis-targeted therapeutics. We will strive to further accelerate global clinical development programs of these novel therapeutics to benefit patients in China and around the world as early as possible."

Those abstracts to be presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting are as follows (two abstracts on APG-115 are simultaneously published in a separate press release):

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Format: Oral Presentation
Abstract: #7502
Time: 11:30 – 14:30 EDT, June 7, 2021
Session Track: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Highlights:
This first-in-human global Phase I study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high tumor lysis syndrome (TLS) risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.
As of January 7, 2021, 35 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15), multiple myeloma (MM, n=6), follicular lymphoma (FL, n=5), Waldenström macroglobulinemia (WM, n=4); and either acute myeloid leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndromes (MDS), or hairy cell leukemia (HCL) (n=1 each).
Lisaftoclax was well tolerated, with manageable adverse events (AEs). No dose-limiting toxicity (DLT) was observed even at the maximum dose of 1,200 mg. The MTD has not been reached, and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in over 10% patients included neutropenia and anemia, while nonhematologic TRAEs included fatigue, diarrhea, and nausea.
12 of 14 evaluable patients with R/R CLL/SLL achieved partial response (PR), for an ORR of 85.7% and a median time to response of 3 treatment cycles (range: 2-7). Absolute lymphocyte counts (ALCs) were reduced at lisaftoclax doses as low as 20 mg/day.
The preliminary PK profile showed that exposures increased with lisaftoclax doses from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples, which were consistent with rapid clinical reductions in ALCs.
In conclusion, efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

Format: Poster Presentation
Abstract: #TPS8589
Time: 09:00 EDT, June 4, 2021
Session Track: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Highlights:
This open-label, multicenter Phase Ib/II study is assessing the safety of preliminary efficacy of pelcitoclax in combination with paclitaxel in patients with R/R SCLC.
Pelcitoclax is being administered by intravenous (IV) infusion on Days 1, 8, and 15, with paclitaxel at the fixed-dose of 80 mg/m2 on Days 1 and 8 of a 21-day cycle.
The primary endpoints of the Phase Ib part of this study include MTD and RP2D. The efficacy of pelcitoclax combined with paclitaxel will be determined in the Phase II part of the study using a Simon two-stage design, with ORR as the primary endpoint. Other endpoints of the Phase II study include PK, progression-free survival, and overall survival.
This study was designed to enroll 58 patients. As of February 8, 2021, 15 patients have been enrolled.
About Lisaftoclax (APG-2575)

Lisaftoclax is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. At present, lisaftoclax has been cleared and approved to enter multiple Phase Ib/II studies in the US, China, and Australia, and is being developed globally for the treatment of multiple hematologic malignancies.

About Pelcitoclax (APG-1252)

Pelcitoclax is a novel, highly potent, small-molecule drug designed to restore apoptosis through selective inhibition of Bcl-2 and Bcl-xL proteins. Multiple Phase Ib/II studies of pelcitoclax as a single agent or in combinations for the treatment of a range of advanced tumors, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), are being conducted in China, Australia, and the US.

On May 19, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, MasterKey therapies, reported initial data from the Phase 1 dose-escalation portion of the MasterKey-01 trial of BDTX-189 in patients with advanced solid tumors harboring any one of more than 48 oncogenic alterations in the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) oncogenes (Press release, Black Diamond Therapeutics, MAY 19, 2021, View Source [SID1234580337]). These data provide early proof-of-concept for BDTX-189, including evidence of anti-cancer activity and a safety profile that is in-line with the Company’s preclinical expectations. The data announced today will be presented in poster presentations at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8, 2021.

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"These encouraging Phase 1 safety and anti-cancer activity data provide early proof-of-concept for BDTX-189 as a differentiated MasterKey inhibitor of undrugged oncogenic mutants of EGFR, including EGFR Exon 20 insertion mutations and oncogenic mutants of HER2," said Rachel Humphrey, M.D., Chief Medical Officer of Black Diamond Therapeutics. "We look forward to the continued advancement of BDTX-189 through clinical development and remain on track to initiate the potentially pivotal Phase 2 portion of the MasterKey-01 trial in the second half of 2021."

"These initial data suggest BDTX-189 may provide meaningful clinical benefit to patients with advanced solid tumors, including those with allosteric EGFR and HER2 mutations," said Alison Schram, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center. "The favorable tolerability profile demonstrated thus far supports the potential of BDTX-189 to address the unmet need in this patient population, for which there are no currently approved targeted therapies and where other in-clinic agents are limited by toxicity."

MasterKey-01 Part A Dose-Escalation Study Design

Part A is a Phase 1, first-in-human, open-label dose escalation study, comprised of initial single-patient, accelerated titration cohorts followed by multiple-patient cohorts utilizing a Bayesian Optimal Interval (BOIN) design. Part A is designed to determine the recommended Phase 2 dose and schedule for the QD and twice-daily (BID) regimens in patients with solid tumors with an allosteric HER2 or HER3 mutation; EGFR or HER2 Exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or EGFR Exon 19 deletion or L858R mutation.

Initial Study Results

As of the data cut-off date of April 2, 2021, 55 patients from the QD regimen were dosed across the dosing range, 25-400 mg QD fasting (n = 12), 800 mg QD fasting (n = 21), 800 mg QD non-fasting (n = 9), 1000 mg QD fasting (n = 7), and 1200 mg QD fasting (n = 6). The dose-escalation portion successfully enrolled patients with a broad range of tumor types and genomic alterations. Tumor types enrolled included non-small cell lung cancer (NSCLC), breast, colorectal (CRC), ovary, biliary, pancreas, cervical, cancer of unknown primary, kidney, salivary, prostate, signet ring cell, liver, and bladder. Genomic alterations enrolled included HER2 amplification and the following mutations: allosteric HER2, EGFR Exon 20 insertion, HER2 Exon 20 insertion, EGFR Exon 19 del./L858R, and HER3.

PK

The PK data for the BDTX-189 QD regimen demonstrated dose-dependent increases in exposure up to 800 mg QD, achieving the predicted efficacious exposure at 800 mg QD. BDTX-189 was rapidly absorbed, with a short elimination half-life of 1.3-4.4 hours, consistent with preclinical predictions. No apparent accumulation or change in exposure at steady state was observed.

Safety

BDTX-189 demonstrated a favorable tolerability profile, with no dose-limiting toxicities at doses of ≤800 mg QD fasting and non-fasting in the dose-escalation cohorts. 800 mg non-fasting was selected as the preliminary RP2D for the QD regimen.

The most common drug-related adverse events were gastrointestinal in nature, the majority of which were low grade and generally medically manageable. At 800 mg QD fasted or non-fasted (n = 30), the most common drug-related adverse events were diarrhea (50%, 7% Gr3), nausea (50%, 7% Gr3), vomiting (30%, 3% Gr3), ALT increased (20%, 10% Gr3), AST increased (13%, 3% Gr3), fatigue (20%, 0% Gr3), skin disorders (13%, 0% Gr3), and decreased appetite (10%, 0% Gr3).

Efficacy

In a heavily pre-treated patient population, including patients who had received prior EGFR/HER2 tyrosine kinase inhibitors (TKI), evidence of anti-cancer activity was observed. Among all cancer type/genomic alteration pairs, two had ≥ three RECIST-evaluable patients dosed at ≥800 mg QD: NSCLC harboring either EGFR Exon 20 mutations (n = 3) or HER2 Exon 20 mutations (n = 3). In the separate group of patients with solid tumors harboring HER2-amplification, six patients dosed at ≥800 mg QD were evaluable by RECIST.

Three patients with NSCLC EGFR Exon 20 dosed at ≥800 mg QD (all at 800 mg QD) were evaluable by RECIST at the time of data cut-off, all of whom had received prior EGFR/HER2-targeted therapy. One confirmed partial response was observed in a patient who had previously responded and then progressed on poziotinib (at the data cut-off, 53% tumor regression observed and treatment with BDTX-189 ongoing 13+ weeks). One patient with stable disease and one patient with progressive disease were observed.
Three patients with NSCLC HER2 Exon 20 dosed at ≥800 mg QD (all at 800 mg QD) were evaluable by RECIST at the time of data cut-off, two of whom had received prior EGFR/HER2-targeted therapy. All three patients demonstrated stable disease.
Six patients with HER2-amplification across a range of tumor types dosed at ≥800 mg QD were evaluable by RECIST at the time of data cut-off, two-thirds of whom had received prior EGFR/HER2-targeted therapy. One confirmed partial response (cancer of unknown primary; at data cut-off, 90% tumor reduction and treatment with BDTX-189 ongoing 24+ weeks), one unconfirmed partial response (NSCLC), two patients with stable disease (ovarian and pancreatic), and two patients with progressive disease were observed.
"We’re incredibly encouraged by the rapid progress of the MasterKey-01 study and promising proof-of-concept data for BDTX-189. These preliminary data support the differentiated profile of BDTX-189 as a MasterKey inhibitor of diverse oncogenic alterations in EGFR and HER2, as well as initial validation of Black Diamond’s proprietary MAP drug discovery engine and MasterKey approach to drug development," said David M. Epstein, President and Chief Executive Officer of Black Diamond Therapeutics. "We’d like to thank all the patients, their families, and their caregivers for participating in this study."

Black Diamond is continuing to dose patients in the ongoing QD dose-escalation portion and the food effect cohort, as well as enrolling and dosing patients in the BID dose-escalation portion. The Company will initiate the safety expansion cohort ahead of the Phase 2 portion of the MasterKey-01 study, which remains on track for initiation in the second half of 2021.

Part B is a Phase 2, open-label, multi-center study designed to determine anti-cancer activity and safety in adult patients with solid tumors harboring an allosteric HER2 mutation or EGFR or HER2 Exon 20 insertion mutation. This portion of the trial will enroll patients in focused tumor/mutation cohorts and is designed to be potentially pivotal. Additionally, based on early proof-of-concept data, Black Diamond is exploring the potential for further clinical development in the HER2-amplified setting.

The data announced today will be presented in poster presentations at the upcoming ASCO (Free ASCO Whitepaper) meeting:

Title: Safety and Preliminary Efficacy from the Phase 1 Portion of MasterKey-01: A First-in-Human Dose-Escalation Study to Determine the Recommended Phase 2 Dose (RP2D), Pharmacokinetics (PK), and Preliminary Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB mutations, in Patients with Advanced Solid Malignancies
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3086

Title: Clinical pharmacokinetics of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3097

Conference Call and Webcast:

In connection with today’s announcement, Black Diamond’s management team will host a conference call and live audio webcast at 6:00 PM ET today, Wednesday, May 19, 2021.

The live audio webcast and accompanying slides may be accessed through the Events page in the Investors section of the Company’s website at www.blackdiamondtherapeutics.com. Alternatively, the conference call may be accessed as follows:

For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website.

About BDTX-189

BDTX-189 is an orally available, irreversible, and ATP competitive small molecule inhibitor that is designed to block the function of a family of oncogenic epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) proteins across a range of tumor types. BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar oncogenic mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of EGFR and HER2. BDTX-189 is also designed to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current EGFR/HER2 kinase inhibitors. Currently, there are no medicines approved by the U.S. Food and Drug Administration (FDA) to target all of these oncogenic mutations with a single therapy.

BDTX-189 is currently being evaluated in a Phase 1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors expressing a range of alterations of EGFR and HER2 receptors, including oncogenic MasterKey mutations, HER2-WT amplification, HER3 mutation, EGFR Exon 19 deletion, and L858R mutation who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the FDA granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.