vadastuximab talirine (SGN-CD33A) / Pfizer - LARVOL DELTA

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN ACUTE MYELOID LEUKEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Agents included Guadectiabine 28%, Magrolimab 7% Alvocidib 3%, Enasidenib 23%,, Flotetuzumab 4%, Vadastuximab 9%, Mitoxantrone 9%, Pevonedistat 2%, Entospletinib 3%, Eprenetapopt 20%, Belinostat 0.5%, Onvansertib 3%, Panobinostat 2%, Cediranib Maleate 1%, Nilotinib 2%, Emavusertib 0.5%, and anti-CD45 antibody (DOTA-BC8) 0.5%. The conventional therapies were azacitidine 20% and cytarabine 17%... This study shows the promising efficacy of novel agents in AML and highlights the need for further prospective trials with larger patient populations to better understand the efficacy and safety outcomes of these agents in patients with AML."

Combination therapy • Monotherapy • Retrospective data • Review • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • TP53

A PHASE 1B STUDY OF THE COMBINATION OF VADASTUXIMAB TALIRINE AND 7+3 INDUCTION THERAPY FOR PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) (EHA 2017) - P1b; "This phase 1b study (NCT02326584) evaluated the safety and antileukemic activity of escalating doses of 33A on 2 schedules: split dose (D1 and 4) or single dose (D1) with 7+3 induction therapy (cytarabine 100 mg/m2 and daunorubicin 60 mg/m2).33A can be safely combined with 7+3 with acceptable count recovery in this population at the doses and schedules studied. Extramedullary AEs, including hepatotoxicity, and induction mortality rates were similar to reported rates for 7+3 alone in this AML population. A high remission rate with the 1st induction cycle was observed, the majority of which were MRD negative."

Clinical • P1 data • Acute Myelogenous Leukemia • Biosimilar • Colorectal Cancer

CD33 SNP Genotype and Splice Variation Are Associated with CD33 Cell Surface Expression and SGN-CD33A Pharmacokinetics (ASH 2018) - P1, P3; "...Expression of CD33 is in part mediated by splicing of the CD33 transcript, and has been demonstrated to be one of the factors that may mediate response to the ADC gemtuzumab ozogamicin, which results in significant benefit in some patients but lacks responses in others...We analyzed CD33 genotype variation in bone marrow (BM) or peripheral blood (PB) samples from patients treated with SGN-33A as either monotherapy (NCT01902329; n=133) or in combination with hypomethylating agents (HMAs; NCT02785900; n=83)...We show that CD33 SNP genotype is associated with CD33 expression, with CC patients demonstrating higher CD33 as detected by flow cytometry; and that CD33 SNP genotype affects the PK profile of SGN-CD33A, with TT patients having higher levels of drug exposure. Our findings suggest that the CD33 genotype can impact CD33 expression, PK profile, and trafficking of bound agents and thus may impact therapeutic targeting of CD33-directed agents."

IO biomarker • PK/PD data • Acute Myelogenous Leukemia • Biosimilar

VADASTUXIMAB TALIRINE PLUS HYPOMETHYLATING AGENTS (HMA): A WELL-TOLERATED REGIMEN WITH HIGH REMISSION RATE IN FRONTLINE OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) (EHA 2017) - P1,P3; "One dose of 33A (10 mcg/kg) was administered outpatient IV every 4 weeks on the last day of HMA (azacitidine or decitabine [5-day regimen], standard dosing). 33A+HMA is well tolerated with a safety profile consistent with on-target myelosuppression. The CR+CRi rate of 76% and low early mortality in older AML patients with poor risk factors is particularly encouraging, and activity appears markedly improved compared to the historical experience of HMA monotherapy. The MRD clearance rate among responding patients who received 33A+HMA is higher than the rate observed with single agent HMAs."

Clinical • Acute Myelogenous Leukemia • Biosimilar • Venous Thromboembolism

CASCADE: A phase 3, randomized, double-blind study of vadastuximab talirine (33A) versus placebo in combination with azacitidine or decitabine in the treatment of older patients with newly diagnosed acute myeloid leukemia (AML). (ASCO 2017) - P3; "Combination treatment may be repeated every 4 weeks until disease progression, leukemic recurrence, or unacceptable toxicity. Study enrollment began in June 2016."

Combination therapy • Head-to-Head • P3 data • Acute Myelogenous Leukemia • Biosimilar

Assessment of myeloblast CD33 receptor occupancy (RO) by vadastuximab talirine in patients with acute myeloid leukemia (AML) receiving monotherapy treatment (AACR 2017) - "Abstract embargoed at this time."

Clinical • Monotherapy • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Oncology

Beyond gemtuzumab ozogamicin: A systematic review of antibody therapies for acute myeloid leukemia. (ASCO 2022) - "gave a combination of talacotuzumab (anti-CD123 antibody) + decitabine to AML patients and reported an ORR of 27% (42/157) in the talacotuzumab + decitabine arm...studied flotetuzumab (anti-CD3 x anti-CD123 DART) and reported an ORR of 30% (9/30) in patients treated at the recommended phase two dose...noticed a CR in 26% (30/117) of patients who received a combination of vadastuximab talirine (anti-CD33 ADC) with azacytidine/decitabine...reported an ORR of 14% (5/32) in the lirilumab + azacytidine arm...administered nivolumab (anti-PD1 antibody) + azacytidine and noticed an ORR of 33% (23/70)...reported that the durvalumab (anti-PD-L1 antibody) + azacytidine arm had a lower ORR than the control arm (31% vs 35%)... Antibody-based therapies are showing great promise for the treatment of AML but are associated with various adverse effects. More prospective clinical trials are needed to further assess the long-term benefits of such medications.AE: adverse events; GI:..."

Review • Acute Myelogenous Leukemia • Gastrointestinal Disorder • Hematological Malignancies • Inflammation • Leukemia • Oncology • CD123

[VIRTUAL] Antibody-Based Therapy in AML: Antibody–Drug Conjugates and Bispecific Agents (SOHO 2021) - "The CD33 ADC vadastuximab talirine, incorporating a synthetic DNA crosslinking pyrrolobenzodiazepene dimer as the cytotoxic agent revealed a promising response rate in R/R AML.11 The combination of this ADC with hypomethylating agents (HMA) in untreated patients achieved a CR/CRirate of approximately 70%, with high proportion of remissions being MRD-negative.12 Unfortunately, a subsequent placebo-controlled phase 3 randomized study comparing HMA versus the combination was discontinued due to increased mortality, likely due to increased marrow suppression in the ADC-containing arm. Another ADC advancing under clinical study is the CD123-targeting IMGN632, an antibody linked to an indolinobenzodiazepine pseudo-dimer...The CD123-targeting DART agent flotetuzumab was studied as salvage treatment in patients in R/R AML, in whom it led to promising single agent composite remission rate...Bispecific agents and ADCs targeting a variety of cell surface antigens in AML have shown..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • FLT3 • PTPRC • WT1

[VIRTUAL] Novel Combination Drug Regimens Using Hypomethylating Agents in Treatment of Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia (ASH 2020) - "For patients who are not candidates for intensive chemotherapy, outcomes in terms of complete response/complete response with incomplete hematologic response (CR/CRi) and median overall survival (mOS) have been evaluated using hypomethylating agents(HMA) including azacytidine (AZA)(CR/CRi=18-27.8%, mOS=10.4-24.5 months) and decitabine (CR/CRi= 18-47%, mOS= 7-7.8 months)...Drugs used in combination included gemcitabine ozagamicin (n=40, CR/CRi =45%, mOS= 7 m), cladribine and low dose cytarabine (n=118, CR/CRi= 68%, mOS =13.8 m), vadastuximab talirine (n=53, CR/CRi=70%, mOS=11.3 m) and selinexor (n=5, CR/Cri= 80%) . In addition, three studies compared outcomes of CDR involving decitabine with all trans retinoic acid (ATRA)(n=93, ORR=21.9% vs 13.5%, p=0.06; mOS= 8.2 m vs 5.1 m, p=0.006) or talacotuzumab (CR/CRi= 15% vs 11%, p=0.44; mOS= 5.36 m vs 7.26 m, p=0.78) or bortezomib (CR/CRi= 39% vs 38%, p=0.91, mOS=9.3 m vs 8.9,p=0.18) to decitabine alone...Drugs included..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CD33-Targeted Therapies: Beating the Disease or Beaten to Death? (PubMed, J Clin Pharmacol) - "Gemtuzumab ozogamicin was the first and only CD33-directed antibody-drug conjugate to be US Food and Drug Administration approved for AML...Promising new strategies include cellular therapy mechanisms and linker molecules. This is an exciting target that requires a considerable amount of precision to yield clinical benefit."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) dimers for cancer therapy. (PubMed, Expert Opin Biol Ther) - "The clinical experience with the twenty PBD dimer-containing ADCs to enter the clinic is reviewed, with a focus on vadastuximab talirine and rovalpituzumab tesirine, both of which were discontinued following pivotal studies, and loncastuximab tesirine and camidanlumab tesirine which are progressing towards approval. Reviewing the clinical efficacy and safety data from almost forty clinical trials of PBD dimer-containing ADCs highlights the complexities and challenges of ADC early clinical development. It enables some conclusions to be made about reasons for failure and suggests strategies to optimise the future clinical development of this promising class of ADCs in a rapidly expanding field."

Journal • Oncology

How can one optimize induction therapy in AML? (PubMed, Best Pract Res Clin Haematol) - "Induction therapy for acute myeloid leukemia has not changed much since 1973, when the 7 + 3 regimen of cytarabine and daunorubicin was born...Recently, two novel agents, CPX-351 and gemtuzumab ozogamicin, have been approved by the US Food and Drug Administration. This review discusses each of the induction strategies and their impact on patient outcomes."

Journal • Review • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

CD33 splice site genotype was not associated with outcomes of patients receiving the anti-CD33 drug conjugate SGN-CD33A. (PubMed, J Hematol Oncol) - "We tested whether a single nucleotide polymorphism (SNP) that affects splicing of CD33 predicted response to treatment in adults with acute myeloid leukemia (AML) who received the novel CD33 antibody-drug conjugate SGN-CD33A. This genotype, for the CD33 splice site SNP rs12459419, was not associated with clinical response (30% CR/CRi in both groups), event-free survival, or overall survival."

Clinical • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients (clinicaltrials.gov) - P1/2; N=14; Active, not recruiting; Sponsor: Seattle Genetics, Inc.; N=102 ➔ 14; Trial primary completion date: Mar 2019 ➔ Feb 2017

Enrollment change • Trial primary completion date • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Seattle Genetics: Q3 2015 Results (Seattle Genetics, Inc) - Anticipated initiation of P1/2 trial for pre-conditioning or post-allogeneic transplant maintenance treatment in patients with AML in H1 2016; Anticipated initiation of P1/2 trial in combination with azacitidine in previously untreated myelodysplastic syndrome in H1 2016

Anticipated new P1/2 trial • Acute Myelogenous Leukemia • Oncology

Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS (clinicaltrials.gov) - P1/2; N=130; Recruiting; Sponsor: Seattle Genetics, Inc.

New P1/2 trial • Biosimilar • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

CASCADE: Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P3; N=500; Not yet recruiting; Sponsor: Seattle Genetics, Inc.

New P3 trial • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Seattle Genetics: Q2 2015 Results (Seattle Genetics, Inc) - Anticipated data from P1 trial (NCT01902329) in combination with hypomethylating agents such as Vidaza and Dacogen for AML in 2015

Anticipated P1 data • Acute Myelogenous Leukemia

SGN-CD33A in combination with hypomethylating agents: A novel, well-tolerated regimen with high remission rate in older patients with AML (EHA 2016) - P1, N=53; NCT01902329; "Thirty-seven of the 49 efficacy evaluable patients (76%) achieved CR (17), CRi (19), or PR (1), with a median time to remission of 2 cycles (range 1 – 4); the median relapse-free survival in CR/CRi patients is currently 6.9 months (range 0+ – 11+). Thirteen of 17 patients (76%) with adverse cytogenetic risk achieved remission. Of the responding patients, 14 of 33 (42%) achieved MRD negativity by local or central flow cytometry."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Seattle Genetics announces more than 20 presentations at ASH 2015 highlighting progress with broad ADCETRIS (brentuximab vedotin) development plan and multiple antibody-drug conjugate (ADC) pipeline programs (Businesswire) - "ADCETRIS data featured in 17 presentations, including eight oral presentations, support goal to establish ADCETRIS as the foundation of therapy for CD30-expressing malignancies; Clinical data for SGN-CD33A (vadastuximab talirine) and SGN-CD19A (denintuzumab mafodotin) ADC programs to be highlighted in oral presentations."

Anticipated clinical data • Anticipated conference • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Seattle Genetics reports third quarter 2014 financial results (Businesswire) - "...financial strength and clinical development progress in the third quarter were marked by record ADCETRIS net sales, up 32 percent from the third quarter of 2013...[Seattle Genetics is] positioned for a strong presence at the upcoming ASH annual meeting with 18 abstracts accepted for presentation... [including] additional data from the AETHERA trial....[The company] will also report interim phase 1 data at ASH from SGN-CD33A and SGN-CD19A...."

Anticipated conference • Anticipated P1 data • Anticipated P3 data • Sales • Hematological Malignancies • Oncology

Seattle Genetics: ASH 2016 (Seattle Genetics, Inc) - "Overall response rate (76%), Deep remissions with a high MRD-negative CRc rate (78%)"

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Seattle Genetics: Annual Report 2014 (Seattle Genetics, Inc) - Anticipated patent expiry of related ADC technology in US and Europe in between 2027 and 2030; Anticipated patent term extension for certain methods of treatment using SGN-CD33A in US and Europe until 2033

Anticipated patent expiry • Acute Myelogenous Leukemia

Seattle Genetics: Clinical Trial Update (Seattle Genetics, Inc) - Anticipated initiation of P2 trial in younger newly diagnosed AML patients in 2017

Anticipated new P2 trial • Hematological Malignancies • Oncology