On December 9, 2023 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve,reported that it will be presenting new data in acute myeloid leukemia (AML) at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Servier, DEC 9, 2023, View Source [SID1234638342]). These data provide a compelling and in-depth look into the treatment patterns and clinical outcomes observed in real-world settings, offering valuable insights for informed decision-making in patient care.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"During our initial five years in the oncology space, Servier has more than doubled its portfolio and launched several new indications for TIBSOVO in IDH1-mutant cancers, including frontline AML, myelodysplastic syndromes (MDS) and previously treated cholangiocarcinoma (CCA) – many of these indications serving as a best-in-class treatment option," said Arjun Prasad," Head of Commercial, Servier Pharmaceuticals. "As the leader driving the science behind targeted mutant IDH inhibition, we strive to maximize the benefits of molecular testing to improve patient outcomes and continue to focus on areas of unmet need where patients could benefit from personalized medicine, from our multiple approvals across hematology and solid tumors to ongoing research in difficult to treat and rare cancers such as chondrosarcoma."

More information on testing for IDH mutations in cancer can be found at IDHlearnmore.com.

Data being presented at ASH (Free ASH Whitepaper) include real-world evidence analysis in patients with newly diagnosed AML (intensive chemotherapy induction ineligible (ICIE) and a susceptible IDH1 mutation comparing Tibsovo in combination with hypomethylating agents (HMA) versus venetoclax in combination with hypomethylating agents. In the analysis of 238 patients, Tibsovo+HMA elicited a higher complete response (CR) rate versus venetoclax+HMA at 42.9% vs. 26.7% (p=0.007). 6-month event-free survival also favored Tibsovo+HMA at 56.0% vs. 39.6% (p=0.044), as well as 11.5% of patients on Tibsovo+HMA achieving bridge to transplant versus 5.0% on a venetoclax+HMA regimen (p=0.066). Median time from diagnosis to start of treatment was 14 versus 20 days for Tibsovo+HMA vs venetoclax+HMA. Treatment discontinuation was 37% for both regimens and toxicity incidence was similar, with the exception of higher febrile neutropenia (FN) rates for venetoclax+HMA versus Tibsovo+HMA (7.9% vs. 1.6%; p=0.009). Patients receiving Tibsovo+HMA had a 61% lower relative risk of unscheduled acute care use in the first 12 weeks (42.9% versus 70.3% for venetoclax+HMA; p<0.001). Venetoclax schedule intensity was also captured, with only 22.8% receiving the full FDA-labeled 28 days of venetoclax during the 28-day cycles; 44.6% did not receive >11 days of venetoclax per cycle. The full analysis will be presented on Monday, December 11 at 4:30 p.m. PST.

"At Servier, we bring the patient voice into everything we do, and our commitment to patients extends far beyond approval," emphasized Becky Martin, PhD, Chief of Medical, Servier Pharmaceuticals. "As a privately held company, we have the ability to invest in the long-term in ways that help to create better understandings on the real-world impact our medicines have on the lives of patients. We’re proud to once again present real-world evidence at ASH (Free ASH Whitepaper), offering the broader oncology community insights into treatment patterns that can help in the development of the best possible treatment regimen for each individual patient."

Additional data being presented at ASH (Free ASH Whitepaper) includes molecular measurable residual disease (MRD) in ICIE patients with newly diagnosed mIDH1 AML treated with Tibsovo+azacitidine, further bolstering the clinical profile of Tibsovo in the front-line setting, as well as real-world analyses examining treatment patterns in both ALL and AML.

On December 9, 2023 TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, reported a poster presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, TScan Therapeutics, DEC 9, 2023, View Source [SID1234638438]). The poster highlights initial data from the Phase 1 multi-arm clinical trial evaluating TSC-100 and TSC-101, which are designed to treat residual disease and prevent relapse following hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphocytic leukemia (ALL) (NCT05473910).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"We are excited to present initial clinical data in our heme program, with six patients in our treatment arms and four patients in our control arm. Complete donor chimerism and MRD negativity, two favorable indicators of treatment success, were achieved and maintained in all six treated patients, four of whom have been on the study for over six months. In contrast, these indicators were not achieved in any of the four control-arm patients. In addition, one of the control-arm patients relapsed at six months, and two other control-arm patients required clinical intervention due to worsening chimerism, a sign of potential future relapse," said Debora Barton, M.D., Chief Medical Officer. "We have now enrolled and dosed patients up to the third and final dose level with no DLTs observed to date and no safety signals thus far, indicating that the third dose level will likely be the recommended Phase 2 dose. After establishing the recommended Phase 2 dose, we plan to open expansion cohorts at that dose to further characterize safety and evaluate translational and efficacy endpoints. There are currently 10 active clinical sites, and additional sites are in the process of being activated to participate in these expansion cohorts."

"Hematopoietic cell transplantation is currently the best treatment option for many patients suffering from AML, MDS, and ALL, as approximately 60% of patients are cured by this procedure," said Gavin MacBeath, Ph.D., Chief Executive Officer. "Unfortunately, for patients who relapse following transplantation, the prognosis is very poor. We have designed TSC-100 and TSC-101 to address this unmet need and increase the success rate of transplantation. We are very encouraged by these early data as they indicate that our therapies are working as designed. The translational data show that our cell therapies are eliminating all residual patient-derived malignant, pre-malignant, and benign cells, which are the cells that drive relapse. We are grateful to all the patients and their families who are participating in this trial and look forward to sharing more data in 2024 as the study continues to enroll."

The Phase 1 trial is a multi-arm dose escalation study evaluating TSC-100, TSC-101, or HCT alone in patients with AML, ALL or MDS undergoing haploidentical allogeneic HCT with reduced intensity conditioning. Patients enrolled in Dose Level 1 receive a single dose of either TSC-100 or TSC-101 approximately 21 days post-transplant. Patients enrolled in Dose Level 2 receive the same dose of TSC-100 or TSC-101 approximately 21 days post-transplant, followed by a second dose administered 40 days after the initial dose. For patients in Dose Level 3, the second dose is escalated four-fold. Primary endpoints include safety and dose-finding, and secondary and exploratory endpoints include relapse rates versus standard-of-care as well as qualitative biological readouts, including MRD and donor chimerism. MRD specifically measures malignant cells, to identify any residual disease present in a patient, and donor chimerism measures a combination of malignant, pre-malignant and normal cells, measuring any remaining patient-derived hematopoietic cells.

Key Poster Highlights:

TSC-100 treatment arm (N=3 T-ALL, AML, AML)

•
3/3 patients treated with TSC-100 achieved complete donor chimerism and MRD negativity.

TSC-101 treatment arm (N=3 TP53 mutated MDS, AML, B-ALL)

•
3/3 patients treated with TSC-101 achieved complete donor chimerism and MRD negativity, including a TP53-mutated MDS patient who remained with no detectable disease for over seven months post-HCT.

•
One patient with AML was MRD-positive following HCT and converted to MRD-negative following treatment with TSC-101.

Four control arm patients (MDS, MDS, TP53-mutated MDS, AML) have been enrolled and received standard of care HCT alone:

•
One TP53-mutated MDS control-arm patient evolved with MRD positivity and worsening mixed chimerism, finally experiencing disease relapse approximately six months after transplantation.

•
Two MDS control-arm patients developed worsening mixed chimerism that prompted early withdrawal of immunosuppression, which was complicated by grade 1 or grade 3 skin graft-vs-host disease.

•
0/4 of the control-arm patients achieved and maintained complete donor chimerism.

Higher sensitivity assays used to detect the activity of T cells:

•
Donor chimerism detected by high-sensitivity next-generation sequencing assay (AlloHeme) with limit of detection 0.13%.

•
MRD detected by next-generation sequencing with limit of detection of 0.05-0.1%.

A copy of the poster can be accessed on the "Publications" section of the Company’s website at www.tscan.com.

Virtual KOL Event

The Company will host a virtual KOL event featuring Monzr M. Al Malki, M.D., on Monday, December 11, 2023, at 8:00 a.m. ET to discuss the data presented at ASH (Free ASH Whitepaper). Dr. Al Malki is an Associate Professor in the Department of Hematology & Hematopoietic Cell Transplantation and Director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant Programs at City of Hope. Details for attending the live event can be found here.

On December 9, 2023 AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB) reported that adult patients with relapsed/refractory (R/R) follicular lymphoma (FL) previously treated with two or more prior therapies experienced strong and durable responses with high overall response (ORR) and complete response (CR) rates when treated with epcoritamab (DuoBody CD3xCD20), an investigational, subcutaneously administered T-cell engaging bispecific antibody (Press release, AbbVie, DEC 9, 2023, View Source [SID1234638343]). More than half of patients who responded to treatment in the study remained responsive to treatment at the time of data analysis (i.e., median duration of response was not reached). Data from the dose-expansion cohort of the Phase 1/2 EPCORE NHL-1 clinical trial are being shared during a poster presentation on Saturday, December 9 at 5:30 PM PT at the ASH (Free ASH Whitepaper) congress in San Diego, California. Updated data from this study include an optimized, step-up dosing schedule showing reduced incidence and severity of cytokine release syndrome (CRS), a notable side effect from immune-engaging cancer treatments.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"Despite treatment advances for patients with follicular lymphoma whose disease has unfortunately progressed, treating relapsed or refractory follicular lymphoma remains highly challenging, particularly as a third-line treatment," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "The patients in this trial represent a historically difficult-to-treat patient population. The data presented today are especially notable because they demonstrated high overall and complete response rates for this investigational therapy and a preview for its potential as a treatment option."

"Further developing epcoritamab as a core therapy to help treat more patients with B-cell malignancies, including follicular lymphoma, is an important goal we share with our partner Genmab," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "These data at this year’s ASH (Free ASH Whitepaper) further build our confidence in epcoritamab’s treatment potential as well as development for earlier patient treatment."

Results from this cohort of 128 adult patients show the following:

At a median follow-up of 17.4 months, ORR, the study’s primary endpoint, was 82%, with a CR rate of 63%; the median time to response and CR were 1.4 months and 1.5 months, respectively.
Among prespecified high-risk subgroups such as patients refractory to prior treatments (double refractory (70%), or refractory to last prior treatment (69%), among others), ORR and CR rates were generally consistent with the overall study population.
Median duration of response and duration of CR were not yet reached.
An estimated 85% and 74% of patients who experienced a CR remained responsive to treatment at 12 and 18 months, respectively.
Additional study data can be found here: (abstract #1655).
No new safety signals were detected. The most common treatment-emergent AE (TEAE) was CRS with 67% occurrence (40% Grade 1, 25% Grade 2, 2% Grade 3). Following an optimized step-up dose regimen in a separate cohort to reduce the risk and severity of CRS, 24 out of 50 patients (48%) experienced grade 1-2 CRS (40% Grade 1, 8% Grade 2, 0% Grade 3). As well, no cases of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported. This data may support investigating optimized step-up dose in an outpatient setting. Additional common TEAEs (>20%) were injection-site reaction (57%), COVID-19 (40%), fatigue (30%), neutropenia (29%), diarrhea (27%) and pyrexia (25%). TEAEs leading to treatment discontinuation occurred in 19% of patients, and death related to TEAEs occurred in 13 patients (10%).

AbbVie and Genmab recently announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to epcoritamab for the treatment of adult patients with R/R FL after two or more therapies. Additionally, the European Medicines Agency (EMA) has validated a Type II application for epcoritamab in the same indication. If approved, R/R FL would become the second conditionally approved indication for epcoritamab in the European Union. More information is available here.

About the Phase 1/2 EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a expansion part, additional patients are being enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The application for BTD included additional data from this cohort of patients. The primary endpoint of the expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints.

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.1 FL is the second most common form of NHL, accounting for 20-30% of all NHL cases, and represents 10-20% of all lymphomas in the western world.1,2,3 Although FL is typically considered an indolent (or slow-growing) lymphoma, it remains incurable with conventional therapy4,5 and patients who achieve remission often experience relapse.6

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.7

Epcoritamab (approved under the brand name EPKINLY in the United States and TEPKINLY in the European Union) has received regulatory approval in adults with certain types of large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), globally. EPKINLY is approved under the FDA’s Accelerated Approval program based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Use of epcoritamab in FL is not approved in the U.S. or in the EU. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigator’s choice chemotherapy, a Phase 3 trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT: 05578976), and a Phase 3 clinical trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat patients with newly diagnosed DLBCL or with FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. USE and IMPORTANT SAFETY INFORMATION

USE

EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more treatments for their cancer.

EPKINLY is approved based on patient response data. A study is ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.

Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.

Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.
Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts. Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. You should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY.
are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea.
These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see the Full Prescribing Information and Medication Guide, including Important Warnings.

On December 9, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported updated data from the Phase 2a trial of investigational zanidatamab, a HER2-targeted bispecific antibody, in combination with palbociclib, a CDK4/6 inhibitor, and fulvestrant, a selective estrogen receptor antagonist, in patients with HER2-positive (HER2+)/HR-positive (HR+) metastatic breast cancer (mBC) as part of a late-breaking oral presentation at the 2023 San Antonio Breast Cancer Symposium (SABCS) (Press release, Jazz Pharmaceuticals, DEC 9, 2023, View Source [SID1234638344]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Data from 51 patients with heavily pretreated HER2+/HR+ mBC (median of 4 prior regimens in the metastatic setting) who were treated with zanidatamab plus palbociclib and fulvestrant demonstrated a progression-free survival at six months (PFS6) of 67% (n=34) [95% confidence interval: 52, 79]. Secondary endpoint findings included a median progression-free survival (mPFS) of 12 months [95% CI: 8, 15] and a confirmed objective response rate (cORR) of 35% [95% CI: 21, 50] with a median duration of response (DOR) of 15 months. The combination regimen was well tolerated with a manageable safety profile.

"Metastatic breast cancer is a particularly aggressive and devastating disease, and patients whose cancer has progressed despite numerous therapeutic interventions are in dire need of additional treatment options – particularly chemotherapy-free options," 1,2 said Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, and primary trial investigator. "Targeting both the HER2 and hormone receptor pathways can be a promising approach for applicable patients, and the durable responses seen in this study signal the potential for this combination to fill a persistent and much needed treatment gap among these patients."3

"The late-breaking data presented at SABCS for zanidatamab in combination with palbociclib and fulvestrant in HER2+/HR+ metastatic breast cancer as a chemotherapy-free treatment option in heavily pretreated patients provide yet another example of the promise this HER2-targeted bispecific antibody holds in the treatment of HER2-expressing cancers where significant unmet needs exist," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "We are encouraged by the meaningful clinical benefit seen in this trial, and we look forward to continuing to advance our broader clinical development program for zanidatamab in breast cancer and other HER2-expressing solid tumors, with the goal of addressing some of the greatest unmet needs in cancer with HER2 expression."

Trial Results

Results of the Phase 2a trial (NCT04224272) presented at SABCS indicate that zanidatamab in combination with palbociclib and fulvestrant, demonstrated meaningful PFS outcomes with a well tolerated safety profile in patients with heavily pretreated HER2+/HR+ mBC.

The single-arm trial evaluated zanidatamab plus palbociclib and fulvestrant in 51 patients with HER2+/HR+ unresectable, locally advanced or metastatic breast cancer who had received prior treatment with at least trastuzumab, pertuzumab, and T-DM1, and no prior treatment with a CDK4/6 inhibitor. Patients treated with the combination regimen received a median of four prior systemic regimens in the metastatic setting (range, 1-12).

Recommended doses of the zanidatamab plus palbociclib and fulvestrant combination therapy were determined in Part 1 of the study. The primary endpoint of Part 2 was PFS6. Other endpoints included mPFS, cORR per RECIST v1.1, DCR and DOR.

At the time of data cutoff (August 3, 2023), treatment with zanidatamab in combination with palbociclib and fulvestrant resulted in a PFS6 of 67% (n=34) and mPFS of 12 months [95% CI: 8, 15]. Median duration of follow-up was 16 months (range, 2-32). Patients treated with the combination regimen achieved a cORR of 35% and DCR of 91%.

Efficacy

All pts (N=51)

PFS6, n (%)

(95% CI)

34 (67)

(52-79)

Median PFS, mo

(95% CI)

12

(8-15)

cORR, n (%)

(95% CI)

16 (35)

(21-50)

Confirmed best overall response (cBOR), n (%)

Complete Response

Partial response

SD

PD

3 (6)

13 (28)

26 (56)

4 (9)

DCR, n (%)

(95% CI)

42 (91)

(79-98)

Median DOR, mo

(95% CI)

15

(12-25)

Zanidatamab plus palbociclib and fulvestrant was well tolerated with a manageable safety profile. One serious treatment-related AE (transaminases increased) was reported (which resolved). No treatment-related deaths were reported. The most common treatment-related AEs (>20% of patients) were diarrhea, neutrophil count decrease/neutropenia, nausea, stomatitis, anemia, vomiting and asthenia. One patient discontinued the combination treatment due to an AE; three patients discontinued palbociclib due to an AE.

The abstract is available to conference registrants on the SABCS conference website here. (Abstract Number LBO1-04).

Additional data being presented at SABCS for zanidatamab include a spotlight poster presentation highlighting positive results of an investigator-sponsored Phase 1 trial evaluating neoadjuvant single-agent zanidatamab in patients with stage 1 node-negative HER2+ breast cancer (Abstract Number PS09-03).

About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

In this Phase 2a trial, zanidatamab is being explored in combination with palbociclib under a clinical trial and supply agreement with Pfizer Inc.

On December 9, 2023 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported a poster presentation at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition featuring follow-up data from its Phase 1 clinical trial that evaluates NKX101 in patients with relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, Nkarta, DEC 9, 2023, View Source [SID1234638329]). NKX101 is an allogeneic, off-the-shelf NK cell therapy candidate derived from healthy donors and engineered to target NKG2D ligands.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

As reported in June 2023, of those patients who received NKX101 after a disease-specific lymphodepletion (LD) regimen comprising fludarabine and cytarabine (Flu/Ara-C), four of six achieved CR/CRi. In the follow up presented today, three of those four patients remained in CR/CRi at 4 months from treatment with NKX101. No cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) of any grade were observed in these patients.

"While this data set is small, we’re encouraged to see responses and early durability in patients with high-risk features, including those who have relapsed after stem cell transplantation. Recent progress in therapy for r/r AML has been limited to targeted therapies, which only help a minority of patients. This all-comers study seeks to help patients without targetable mutations as well as those for whom these treatments are ineffective," noted David R. Shook, MD, Chief Medical Officer of Nkarta. "We continue to evaluate NKX101 following Flu/Ara-C in this high-need patient population."

Nkarta plans to provide an update from the NKX101 Flu/Ara-C LD cohort in the first half of 2024 that includes preliminary safety and response data from 12 to 20 additional patients.

Nkarta’s 2023 ASH (Free ASH Whitepaper) poster will be available for download shortly after its scheduled presentation at View Source

About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with a membrane-bound form of interleukin-15 (IL15) for greater persistence and activity without exogenous cytokine support.