enapotamab vedotin (HuMax-AXL-ADC) / Genmab, Pfizer - LARVOL DELTA

Evaluating the potential of radiomics features to predict outcome to an antibody-drug conjugate therapy in non-small cell lung cancer patients (AACR 2024) - P1/2 | "This study evaluated radiomics, a non-invasive biomarker, for assessment of tumor heterogeneity in non-small cell lung cancer (NSCLC) patients treated with an AXL-targeting antibody-drug conjugate (ADC), enapotamab vedotin (EnaV), through analyzing baseline and post-treatment radiomic features from CT images for predicting outcome.Clinical development of EnaV was discontinued in 2020 due to low response rates unimproved by dose optimization and/or predictive biomarkers...Cancer Res. 2021"

Biomarker • Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • AXL

Enfortumab Vedotin continues to show promise as neoadjuvant therapy for MIBC (Urology Times) - "'All patients were able to undergo surgery with no delays due to neoadjuvant enfortumab vedotin–related [AEs] in this understudied population,' lead study author Thomas W. Flaig...emphasized in a poster of the data."

Media quote

Enapotamab Vedotin, an AXL-Specific Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Patient-Derived Xenograft Models of Soft Tissue Sarcoma. (PubMed, Int J Mol Sci) - "Doxorubicin (doxo) remains the standard of care for patients with advanced soft tissue sarcoma (STS), even though response rates to doxo are only around 14% to 18%. One model was found negative for AXL on experimental passage and did not respond to EnaV. This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of AXL-expressing sarcomas."

Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Transplantation • AXL

Bladder Cancer Drug Shows Antitumor Activity in Cisplatin-Ineligible Patients (Cancer Therapy Advisor) - "Neoadjuvant treatment with enfortumab vedotin (EV) monotherapy has promising antitumor activity in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy, according to initial results from a phase 1b/2 trial presented at the ASCO Genitourinary Cancers Symposium 2022. The findings are important because no standard of care exists for neoadjuvant treatment in this patient population, according to principal investigator Daniel P. Petrylak, MD..."

"Dr. @HosseinBorghaei @FoxChaseCancer discussed ADCs for AXL (Enapotamab Vedotin, BA3001), ROR, and protein tyrosine kinase 7 (PTK7) (PF-06647020) for treatment of #lungcancer at #TTLC22. @lcrf_org" (@EugeneManley)

Lung Cancer • Oncology • Solid Tumor • AXL

Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=306; Completed; Sponsor: Genmab; Active, not recruiting ➔ Completed; Trial primary completion date: Aug 2021 ➔ Nov 2021

Clinical • Trial completion • Trial primary completion date • Cervical Cancer • Endometrial Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Thyroid Gland Carcinoma • MUC16

First-in-human, dose-escalation, phase (ph)I trial to evaluate safety of anti-Axl antibody-drug conjugate (ADC) enapotamab vedotin (EnaV) in solid tumors. (ASCO 2019) - P1/2; "The RP2D of single agent EnaV in pre-treated pts with solid tumors was 2.2 mg/kg 1Q3W. EnaV had encouraging preliminary anti-tumor activity and will be evaluated in 7 ph2a expansion cohorts to further assess safety, tolerability, PK, anti-tumor activity and Axl expression. Funding: Genmab A/S."

Clinical • P1 data

First-In-Human Phase 1/2 Trial of Anti-AXL Antibody–Drug Conjugate (ADC) Enapotamab Vedotin (EnaV) in Advanced NSCLC (IASLC-WCLC 2019) - P1/2; "In this high unmet need patient population, with advanced EGFR WT and ALK- NSCLC who are pretreated with PD-1/PD-L1 inhibitors and platimum-based therapies, EnaV monotherapy demonstrated a manageable safety profile and encouraging preliminary clinical activity. This cohort has expanded to allow up to 60 patients to gain further knowledge of AXL as a potential biomarker for responsiveness to EnaV and to gather additional data on safety and efficacy. Funding: Genmab A/S"

IO Biomarker • P1/2 data • PD(L)-1 Biomarker

Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=374; Active, not recruiting; Sponsor: Genmab; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2021 ➔ Dec 2021; Trial primary completion date: Feb 2021 ➔ Aug 2021

Enrollment closed • Trial completion date • Trial primary completion date • Cervical Cancer • Endometrial Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Thyroid Gland Carcinoma

Cooperative targeting of immunotherapy-resistant melanoma and lung cancer by an AXL-targeting antibody-drug conjugate and immune checkpoint blockade. (PubMed, Cancer Res) - "Here we show that enapotamab vedotin (EnaV), an antibody-drug conjugate (ADC) targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models...Combining EnaV with tumor-specific T cells proved superior to either treatment alone in models of melanoma and lung cancer and induced ICB benefit in models otherwise insensitive to anti-PD-1 treatment. Our findings indicate that targeting AXL-expressing, immunotherapy-resistant tumors with EnaV causes an immune-stimulating tumor microenvironment and enhances sensitivity to ICB, warranting further investigation of this treatment combination."

Checkpoint inhibition • IO biomarker • Journal • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Oncology • Solid Tumor • AXL

[VIRTUAL] The making of an ADC (SABCS 2020) - "In the road-map to developing an ADC, understanding target biology and selecting the most optimal antibody, linker and toxic payload represent critical parameters. This talk will provide an overview of this thought process in the context of the development of two ADCs currently in the clinic, tisotumab vedotin and enapotamab vedotin."

Breast Cancer • Oncology

Genmab Accelerates Priority Candidates, Ends Enapotamab Vedotin Development (Scripintelligence) - "...Genmab has dropped the AXL targeted antibody-drug conjugate, enapotamab vedotin from early clinical development..."

Discontinued • Oncology

"Enapotamab vedotin $GEN discontinued yesterday. cf $BGBIO.OL" (@JacobPlieth)

"$GMAB Genmab Announces Enapotamab Vedotin Update https://t.co/R9PnAi4wFO" (@otcdynamics)

Genmab Announces Enapotamab Vedotin Update (Genmab Press Release) - "Genmab A/S...announced...that it will not advance the development of enapotamab vedotin. While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept."

Discontinued • Oncology

Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer. (PubMed, JCI Insight) - "Enapotamab vedotin also showed antitumor activity in vivo in 3 EGFR-mutant, EGFR inhibitor-resistant PDX models, including an osimertinib-resistant NSCLC PDX model. In summary, enapotamab vedotin has promising therapeutic potential in NSCLC. The safety and preliminary efficacy of enapotamab vedotin are currently being evaluated in the clinic across multiple solid tumor types, including NSCLC."

IO Biomarker • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Expert expands on evolving treatment strategies for prostate and urothelial cancers - "...Tanya Dorff, MD...discussed evolving practices in prostate and urothelial cancers as well as highlighted controversies in the treatment landscape such as the role of combination therapy in prostate cancer....Dorff went on to explain that for now, combination therapy for prostate cancer has yet to be proven effective or more beneficial than single-agent therapy....Checkpoint blockade may also make its way into the armamentarium of physicians who treat prostate cancer in patients with microsatellite instability....These trials are evaluating new and novel therapeutic options to improve survival in patients with these diseases."

Combination therapy

Enapotamab Vedotin (IASLC-LCTT 2020) - No abstract available

Cooperative targeting of immunotherapy-resistant melanoma and lung cancer models by an AXL-targeting antibody-drug conjugate and immune checkpoint blockade (SITC 2019) - "We and others previously reported that the receptor tyrosine kinase AXL is a critical resistance marker to targeted therapy in melanoma and lung cancer [3,4], and that AXL-positive cell fractions can be effectively eliminated by an AXL-targeting antibody-drug conjugate (enapotamab vedotin, EnaV [5])... Our findings demonstrate that EnaV and immunotherapy cooperatively exert a strong anti-tumor response in therapy-refractory melanoma and lung cancer models. Importantly, even in models fully refractory to either T cells and/or anti-PD1, EnaV treatment restores sensitivity to promote tumor elimination. Together, these results indicate that targeting AXL-positive, immunotherapy-resistant tumor fractions with EnaV enhances ICB sensitivity, thus warranting further investigations into this combination in a clinical setting."

Checkpoint inhibition • IO Biomarker • PD(L)-1 Biomarker • Preclinical

First-in-human trial of anti-AXL antibody-drug conjugate in advanced lung cancer (JNCCN 360) - "AXL, a transmembrane receptor tyrosine kinase, 'is aberrantly expressed in various cancers and associated with poor prognosis and treatment resistance,' especially resistance to PD-1 immune checkpoint inhibitors, explained...Suresh Ramalingam, MD...This is a 'high unmet-need patient population,' explained Dr. Ramalingam."

Media quote

Identification of certain tumor characteristics enhances immunotherapy response in NSCLC (Targeted Oncology) - "'This was a phase I study with a built-in expansion cohort for patients with advanced-stage NSCLC,' Suresh S. Ramalingam, MD...in an interview. 'After the recommended dose of ENA V was established, we proceeded to enroll patients with advanced-stage NSCLC that had progressed on prior standard therapies. The intent was to evaluate the efficacy of ENA V in this patient population.'"

Interview

"$SGEN $GMAB presenting enapotamab vedotin (HuMax-AXL-ADC) ph1/2 data at #WCLC2019. Relevant for Bergenbio $BGBIO.OL" (@JacobPlieth)

Genmab announces preliminary data to be presented at IASLC 2019 World Conference on Lung Cancer (Genmab Press Release) - P1/2, N=374; NCT02988817; Sponsor: Genmab; "Genmab A/S (Nasdaq: GMAB) announced today that preliminary data from the Phase I/II trial of enapotamab vedotin in advanced non-small cell lung cancer (NSCLC) has been accepted for oral presentation at the International Association for the Study of Lung Cancer 2019 World Conference on Lung Cancer (IASLC 2019 WCLC) taking place from September 7-10, 2019 in Barcelona, Spain."

P1/2 data

"IASLC #WCLC19 program out https://t.co/ooqPASucLz compilation of main plenary/oral/mini-oral titles here https://t.co/UtdLtZUumK $LOXO $LLY LOXO-292, $AZN durva CASPIAN, $GMAB $SGEN enapotamab vedotin, $MRK KN-817, TMB in KN-021 & KN-189 (even $MRK is looking at TMB?!)..." (@BertrandBio)

Genmab announces data to be presented at 2019 ASCO annual meeting (GlobeNewswire) - “Genmab A/S…announced today that 14 industry sponsored abstracts regarding Genmab programs were accepted for presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago from May 31 to June 4, 2019….A list of accepted industry sponsored abstracts is provided below, and includes ten daratumumab abstracts, two of which were accepted for oral presentations, one abstract on enapotamab vedotin, and two abstracts on tisotumab vedotin…We are especially looking forward to the first full presentations of data from the COLUMBA and CASSIOPEIA daratumumab Phase III trials,’…’We are equally excited to begin sharing with the oncology community early data from enapotamab vedotin and ongoing trials in progress for tisotumab vedotin.’”

P1 data • P2 data • P3 data