On December 11, 2023 Affimed N.V. (Nasdaq: AFMD) ("Affimed or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported interim safety and efficacy data on its innate cell engager (ICE) AFM24 from the ongoing AFM24-102 combination study with atezolizumab, an anti-PD-L1 checkpoint inhibitor, in patients with advanced EGFR-expressing solid tumors (Press release, Affimed, DEC 11, 2023, View Source [SID1234638408]). The data update as of December 6th, 2023, includes 15 patients from the EGFR-wildtype NSCLC cohort with a median of 2 prior lines of therapy. Importantly, all patients were pretreated with and ultimately progressed while on PD-[L]1 targeting therapy.

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The combination of AFM24 with atezolizumab showed encouraging signals of clinical activity, including 1 unconfirmed CR, 3 PRs (1 confirmed, 2 unconfirmed) and 7 patients exhibiting SD. All eleven patients with a confirmed response, unconfirmed response or stable disease (73%) are continuing treatment, with 4 patients exceeding 3 months of therapy; 2 patients improved from SD at the first scan to PR at the second scan based on RECIST criteria.

"Most patients with advanced NSCLC will need additional treatment after first-line therapy, and currently available options for patients in the 2L+ setting provide only modest response rates and short progression-free survival," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "Given the severity of this cancer and the urgent need for new treatments, we are very encouraged by the early safety and efficacy results demonstrated by the combination of AFM24 and atezolizumab in this cohort. We look forward to seeing the data in this cohort mature as well as to sharing data from the EGFR-mutant NSCLC cohort, anticipated in the first half of 2024."

Affimed’s ICE AFM24, in combination with atezolizumab, has the potential to reactivate the innate and consequently the adaptive immune system to recognize and destroy EGFR-positive NSCLC tumors. Considering the low ORR reported on atezolizumab monotherapy in checkpoint inhibitor—relapsing and refractory patients, Affimed believes the clinical activity observed in AFM24-102 is likely due to the synergy of AFM24 with atezolizumab.

AFM24 has demonstrated a positive safety and tolerability profile as both a monotherapy and in combination therapy. The combination with atezolizumab has not led to unexpected toxicity, and the toxicity observed to date is in line with the toxicity profile of the individual agents alone. The majority of patients experienced only mild to moderate treatment-related adverse events.

Affimed also announced that it has discontinued enrollment in AFM24-102 into the gastric cancer cohort and the basket cohort evaluating pancreatic cancer, biliary tract cancer and hepatocellular carcinoma. While clinical activity was observed in both cohorts, neither cohort is likely to achieve response rates that would meet the Company’s efficacy hurdle and the Company’s strategic focus is to advance the NSCLC program as fast as possible.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link https://register.vevent.com/register/BIb2258d6c5f5a474cad74869a7b7b1bb5, and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.

About the AFM24-102 Phase 1/2a Study

AFM24-102 is a Phase 1/2a open-label, non-randomized, multicenter, dose escalation, and expansion study evaluating AFM24 in combination with atezolizumab in patients with selected EGRF-expressing advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies (NCT05109442).

The Company also announced data from the phase 1/2 data study of acimtamig in combination with allogeneic NK in relapsed/refractory Hodgkin Lymphoma patients conducted at the University of Texas MD Anderson Cancer Center. The Company will host a call today at 1:30 p.m. PST / 4:30 p.m. EST / 22:30 CET to discuss both the acimtamig and AFM24 clinical data updates and to provide an update on the status of the acimtamig LuminICE-203 study, AFM13-104.

About AFM24

AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

In addition to studying AMF24 in combination with the checkpoint inhibitor atezolizumab, Affimed is also evaluating options for a combination of AFM24 with an allogeneic off-the-shelf NK cell product that the Company expects to be well suited for heavily pretreated patient populations.

On December 11, 2023 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported that the Company will host a conference call on Tuesday, December 12, 2023, at 8:00am ET (Press release, 2seventy bio, DEC 11, 2023, View Source [SID1234638407]). The event will highlight data presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place from December 9-12, 2023, in San Diego.

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Participants can access the conference call live via webcast which will be available on the Investors and Media page of the company’s website at View Source A replay of the call will be available on the 2seventy bio website for 30 days following the event.

ASH Presentation Details
Oral Presentation: Idecabtagene Vicleucel (ide-cel) Versus Standard Regimens in Patients (pts) with Triple-Class Exposed (TCE) Relapsed and Refractory Multiple Myeloma (RRMM): Updated Analysis from KarMMa-3
Presenter: Paula Rodriguez-Otero
Date & Time: Monday, December 11, 4:45pm PT

Poster Presentation: Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in Patients with Clinical High-Risk Newly Diagnosed Multiple Myeloma (MM) with an Inadequate Response to Frontline Autologous Stem Cell Transplantation (ASCT): KarMMa-2 Cohort 2c Extended Follow-up
Presenters: Madhav Dhodapkar; Melissa Alsina
Date & Time: Saturday, December 9, 5:30 – 7:30pm PT

On December 11, 2023 Novartis reported results from the extension period of the pivotal Phase III APPLY-PNH trial of oral monotherapy Fabhalta (iptacopan) in adults with paroxysmal nocturnal hemoglobinuria (PNH) who had residual anemia (hemoglobin <10 g/dL) despite previous anti-C5 therapy (Press release, Novartis, DEC 11, 2023, https://www.novartis.com/news/media-releases/novartis-presents-new-48-week-results-from-phase-iii-apply-pnh-trial-showing-sustained-efficacy-and-long-term-safety-fabhalta-iptacopan-adults-paroxysmal-nocturnal-hemoglobinuria-pnh [SID1234638372]). Continuous Fabhalta treatment (200 mg twice daily) for 48 weeks enabled sustained hemoglobin-level increases to near-normal (12 g/dL or more), blood transfusion avoidance, and reduced patient-reported fatigue in the majority of patients; comparable benefits emerged in those patients switching from anti-C5 therapy to Fabhalta in the extension1. Data will be presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper).

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"The new APPLY-PNH data are an expansion of the robust outcomes we saw in the randomized phase and demonstrate that patients with PNH who took Fabhalta experienced meaningful hemoglobin improvement over the longer term – nearly a year," said principal co-investigator Antonio Risitano, M.D., Ph.D., President of the International PNH Interest Group and Head of the Hematology and Hematopoietic Transplant Unit, Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria at the AORN San Giuseppe Moscati, Avellino, Italy. "Additionally, the new data confirm that these benefits may occur within weeks after switching from anti-C5s. The APPLY-PNH findings continue to confirm Fabhalta as a promising therapeutic option for people living with PNH."

Patients completing the 24-week randomized treatment period of APPLY-PNH could elect to enter the extension, continuing Fabhalta (61/62 patients; one patient discontinued due to pregnancy) or switching from anti-C5s to Fabhalta (34/35 patients; one patient discontinued based on investigator decision) through week 481,2.

In the continuous Fabhalta group, outcomes achieved in the randomized period were sustained at 48 weeks: mean hemoglobin level continued to be near-normal (12.2 g/dL), nearly all patients (91.9%) remained free of transfusions (Weeks 2-48), and improvements in patient-reported fatigue were observed (adjusted mean change from baseline: 9.80-point increase in Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] score)1.

In the anti-C5-to-Fabhalta group, similar benefits emerged after switch: mean hemoglobin levels increased to near-normal (from 9.1 g/dL at 24 weeks to 12.1 g/dL at 48 weeks), transfusion avoidance was achieved for almost all patients (94.1%, Weeks 26-48), and improvements in patient-reported fatigue were observed after switching to Fabhalta (adjusted mean change from baseline between Week 48 and Week 24: 10.79-point increase in FACIT-F score)1.

"Coming on the heels of Fabhalta’s recent approval in PNH, these extended data from the APPLY-PNH phase III trial reinforce Fabhalta’s utility as an important new oral monotherapy for people living with PNH," said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. "We are eager to bring this novel treatment to even more people living with rare complement-driven disorders as we pursue several additional indications for Fabhalta."

Fabhalta had a similar safety profile at 48 weeks vs. 24 weeks1,2. Three patients had major adverse vascular events (MAVEs), all considered unrelated to Fabhalta (one serious transient ischemic attack [TIA] occurred in the randomized period and was reported previously)1,2. In the extension, there was one non-serious TIA and one serious portal vein thrombosis (PVT; this patient had a history of PVT and discontinued heparin prior to the MAVE)1. Six patients of 62 receiving continuous Fabhalta for 48 weeks had clinical breakthrough hemolysis (BTH); one patient in the anti-C5-to-Fabhalta extension arm had clinical BTH after switching (compared to six of 35 patients while on anti-C5s prior to switch)1,2. All cases of clinical BTH resolved without changing Fabhalta dosing1. During the 48-week study period, the most frequently reported treatment-emergent adverse events (TEAEs) in the Fabhalta arm were COVID-19 (29.0% of patients), headache (19.4%), and diarrhea (16.1%)1. Throughout the full 48 weeks on Fabhalta, 9.7% of patients experienced any severe TEAE and 14.5% experienced any serious TEAE, none of which was suspected to be related to Fabhalta treatment; there were no serious hemolysis TEAEs on Fabhalta1,2. There were no serious infections caused by N. meningitidis, S. pneumoniae, or H. influenzae and no treatment discontinuations because of TEAEs1,2.

PNH is a rare, chronic, and serious complement-mediated blood disorder, in which a large proportion of patients can remain anemic and some dependent on blood transfusions despite currently available standard of care, anti-C5 treatments7-10.

Full 48-week results from the Phase III APPOINT-PNH trial in treatment-naïve PNH patients will be presented at a congress in 2024.

About APPLY-PNH
APPLY-PNH (NCT04558918) was a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) for the treatment of PNH by assessing if switching to Fabhalta was superior to continuing on anti-C5 therapies (US-approved and non-US-approved eculizumab or ravulizumab) in adult patients presenting with residual anemia (Hb <10 g/dL) despite a stable regimen of anti-C5 treatment in the last six months prior to randomization4,11. The trial enrolled 97 patients who were randomized in an 8:5 ratio to either twice-daily, oral Fabhalta monotherapy, or intravenous anti-C5 therapies (continuing with the same regimen as they were on prior to randomization)4,11.

About paroxysmal nocturnal hemoglobinuria (PNH) 
PNH is a rare, chronic and serious complement-mediated blood disorder7. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system7,8. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots), fatigue and other debilitating symptoms7,8.
 
It is estimated that approximately 10-20 people per million worldwide live with PNH7. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old12,13,14.
 
PNH has a significant unmet need not addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH remain anemic, and some dependent on blood transfusions7-10,15.

About Fabhalta (iptacopan)
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway14,16,17. Fabhalta is FDA-approved for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).
 
Discovered at Novartis, Fabhalta is currently in development for a range of complement-mediated diseases including immunoglobulin A nephropathy (IgA nephropathy), C3 glomerulopathy (C3G), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS).
 
Based on disease prevalence, unmet needs and data from Phase II studies, Fabhalta has received FDA approval in PNH, FDA Breakthrough Therapy Designation in C3G, orphan drug designations from the FDA and EMA in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN.

On December 10, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported positive final results from the Phase 2 TELLOMAK study in Sézary Syndrome (SS) (Press release, Innate Pharma, DEC 10, 2023, View Source [SID1234638397]). The results were presented at the ASH (Free ASH Whitepaper) 2023 Annual Meeting, in San Diego, California.

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As of May 1, 2023, data cutoff, patients in the Sézary Syndrome cohort (cohort 1, n=56) received a median of 5 prior systemic therapies, including mogamulizumab, and had a median follow-up of 14.4 months.

The data demonstrated that lacutamab showed robust clinical activity and an overall favorable safety profile. The global confirmed objective response rate (ORR) was 37.5% (21/56), including 2 complete responses (CR) and 19 partial responses (PR). Overall response rate (ORR) in the skin was 46.4% (26/56), including 5 CR and 21 PR and ORR in the blood was 48.2% (27/56) with 15 CR and 12 PR. Median progression-free survival was 8.0 months (95% CI 4.7-21.2). In patients who achieved a global response, the median duration of response is 12.3 months (95% CI 5.2-NE).

Best Global Response

N=56

Best Response in Skin

N=56

Best Response in Blood

N=56

Best Response in LN

N=461

Best Response (N, %)

CR

2 (3.6)

5 (8.9)

15 (26.8)

3 (6.5)

PR

19 (33.9)

21 (37.5)

12 (21.4)

6 (13.0)

SD

28 (50.0)

27 (48.2)

24 (42.9)

28 (60.9)

PD

7 (12.5)

3 (5.4)

5 (8.9)

5 (10.9)

NE

0

0

0

4 (8.7)

ORR% [95%CI]

37.5%

[26.0-50.6]

46.4%

[34.0-59.3]

48.2%

[35.7-61.0]

19.6%

[10.7-33.2]

Table 1: Efficacy results in SS patients (n=56)

____________________________________
1 includes patients not involved at baseline who progressed in the LN

"The rapid and durable responses observed in the Phase 2 TELLOMAK trial which enrolled heavily pretreated patients, confirms that treatment with lacutamab achieves clinically meaningful outcomes for patients with Sézary Syndrome after at least two prior systemic therapies," commented Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma. "Enrollment to TELLOMAK study is completed and long-term follow-up will provide more mature data on the key study endpoints in due course."

Prof. Pierluigi Porcu, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, and Principal Investigator in the TELLOMAK study, added: "Sézary Syndrome patients treated with more than two prior systemic therapies including mogamulizumab, represent a high unmet medical need population with poor quality of life. It is promising to see lacutamab achieving remarkable efficacy along with favorable safety in this heavily pre-treated population. We thank the investigators, clinical research coordinators, patients and caregivers involved in the TELLOMAK program."

Innate Pharma will host a virtual KOL event, featuring Prof. Pierluigi Porcu, on lacutamab, highlighting results from ASH (Free ASH Whitepaper) oral presentation on Tuesday, December 12, 2023 at 7:00AM PST (4:00PM CET).

Virtual KOL Event Details

Tuesday, December 12, 2023 at 7:00 AM PST (4:00PM CET)

The live webcast will be available at the following link:

View Source

Participants may also join via telephone using the following registration link:

View Source

This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com. A replay of the webcast will be available on the Company website for 90 days following the event.

About Lacutamab

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphomas of T lymphocytes have a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab is granted European Medicines Agency (EMA) PRIME designation and US Food and Drug Administration (FDA) granted Fast Track designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and in the United States for the treatment of CTCL.

About TELLOMAK

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:

Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.
Cohort 2: lacutamab being evaluated as a single agent in patients with MF that express KIR3DL2, as determined at baseline with a Simon 2-stage design.
Cohort 3: lacutamab being evaluated as a single agent in patients with MF that do not express KIR3DL2, as determined at baseline, with a Simon-2 stage design.
All comers: lacutamab being evaluated as a single agent in patients with both KIR3DL2 expressing and non-expressing MF to explore the correlation between the level of KIR3DL2 expression and treatment outcomes utilizing a formalin-fixed paraffin embedded (FFPE) assay under development as a companion diagnostic.
The trial is now fully enrolled. The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, overall survival, quality of life, pharmacokinetics and immunogenicity and adverse events.

On December 10, 2023 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported new safety and efficacy findings from the newly diagnosed (ND) cohorts of the Phase 1b/2 study of pivekimab sunirine (pivekimab) in combination with azacitidine (Vidaza) and venetoclax (Venclexta), (pivekimab triplet) in patients with ND acute myeloid leukemia (AML) (Press release, ImmunoGen, DEC 10, 2023, View Source [SID1234638396]). These findings will be presented in a poster session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California.

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"Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk"

Post this
"We are pleased to share these new findings at ASH (Free ASH Whitepaper), which demonstrate encouraging anti-leukemia activity of the pivekimab triplet in newly diagnosed AML, a disease in which long-term survival unfortunately remains limited," said Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "The MRD negativity rates, which are indicative of a deep remission, are particularly promising in the treated patient population. This encouraging activity, along with a manageable safety profile, support the continued evaluation of this novel triplet in this setting."

PIVEKIMAB SUNIRINE, A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN COMBINATION WITH AZACITIDINE AND VENETOCLAX IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
Lead Author: Navel Daver, MD
Poster Session: 616 (Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II)
Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 2906

In the open-label, multicenter, Phase 1b/2 study of pivekimab in combination with azacitidine and venetoclax in patients with ND CD123-positive AML, patients received the recommended Phase 2 dose of pivekimab at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 daily on days 1-7, and venetoclax at up to 400 mg for at least 14 days or up to 28 days, based on cohort assignment, in a 28-day cycle. The primary endpoints are complete remission (CR) rate, composite CR rate (CCR [CR+CRh+CRp+CRi]), minimal residual disease (MRD) negativity rate, and duration of remission. Key secondary endpoints are safety, pharmacokinetics, and immunogenicity.

Key findings for 50 ND patients (n=25 per cohort) as of September 29, 2023 (data cut-off) include:

Anti-Leukemia Activity

In the overall population, CCR rate was 68% (34/50), CR rate was 54% (27/50), and MRD negativity rate among evaluable patients achieving CCR was 76% (22/29). MRD was assessed centrally by flow cytometry with <0.1% considered negative. Response rates and MRD negativity were numerically comparable between cohorts 1 and 2, despite differences in the venetoclax schedule.
In a post hoc subset analysis of patients unfit for intensive chemotherapy (i.e. patients >75 years of age, and/or with pre-specified comorbidities) (n=23), CCR rate was 78% (18/23), CR rate was 61% (14/23), and MRD negativity rate was 79% (11/14).
In patients known to be TP53wt (n=25), CCR rate was 88% (22/25), CR rate was 84% (21/25), and MRD negativity rate was 80% (16/20). CCR and MRD negativity rates, respectively, were high across other major molecular subsets, including:
FLT3 (ITD or TKD): 100% (6/6) and 100% (6/6)
IDH1 mutant: 100% (4/4) and 67% (2/3)
IDH2 mutant: 100% (6/6) and 83% (5/6)
NPM1 mutant: 100% (8/8) and 86% (6/7)
K/NRAS mutant: 50% (3/6) and 67% (2/3)
TP53 mutant: 50% (7/14) and 50% (3/6)
Among all MRD negative patients, the median time to MRD negativity was 1.87 months (range: 0.79-5.16 months).
Although follow-up duration was short (median 5.2 months), landmark overall survival estimate at 6 months is 86%.
The study is continuing to enroll newly diagnosed unfit AML patients.
Safety

The triplet displayed a manageable safety profile; no new safety signals were observed compared to previously reported data.
The most common non-hematologic treatment-emergent adverse events (TEAEs) (all grades [grade 3+]) seen in ≥20% of all patients were constipation (48% [2%]), peripheral edema (44% [4%]), diarrhea (40% [2%]), hypophosphatemia (34% [2%]), nausea (32% [4%]), hypokalemia (28% [4%]), fatigue (24% [6%]), hypotension (24% [2%]), and pyrexia (24% [0%]). In the overall population:
Rates of cytopenias were similar to those observed with azacitidine and venetoclax, with a median neutrophil recovery to ≥500/µL and platelet recovery to ≥50,000/µL by day 34 and day 22, respectively.
No veno-occlusive disease, capillary leak syndrome, or sinusoidal obstruction syndrome were observed.
Infusion-related reactions (IRRs) occurred in 16% of patients (0 grade 3+ IRRs).
Discontinuations due to an adverse event (AE) were 4% (2 patients).
30-day mortality was 0%.
60-day mortality was 4% (2 patients; due to pneumonia and early disease progression).
"Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk," said Michael Vasconcelles, MD, ImmunoGen’s Executive Vice President, Research, Development, and Medical Affairs. "We are pleased with the low early mortality and manageable safety profile observed, in particular the lack of prolonged cytopenias. We look forward to continuing to expand our cohort of newly diagnosed unfit patients to inform the development path for pivekimab in AML."

PRECLINICAL POSTERS
ImmunoGen is also presenting two preclinical posters at ASH (Free ASH Whitepaper).

Title: Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models
Presenter: Anna Skwarska
Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III)
Date and Time: Monday, December 11, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 4155

Title: Spatial Response to Pivekimab Sunirine In Vivo in a BPDCN Model
Presenter: Margaux Poussard
Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II)
Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 2791

Additional information can be found at View Source, including abstracts.

ABOUT PIVEKIMAB SUNIRINE
Pivekimab sunirine is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. Pivekimab is currently being evaluated as monotherapy for patients with BPDCN and in combination with azacitidine (Vidaza) and venetoclax (Venclexta) for patients with untreated and relapsed/refractory AML. Pivekimab uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single-strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. The European Medicines Agency (EMA) granted orphan drug designation to pivekimab for the treatment of BPDCN in June 2020. Pivekimab also holds this designation in the US. In October 2020, the FDA granted pivekimab Breakthrough Therapy designation in relapsed/refractory BPDCN.

ABOUT ACUTE MYELOID LEUKEMIA (AML)
AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the US alone, more than 20,000 people will be diagnosed with AML and more than 11,000 will die from the disease this year.

ABOUT CD123
CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a clinically validated therapeutic target.