Subscribe

Advertisement

Other Cancer

Relevant Articles About Research and Clinical Trials in Other Cancer

Stories to Watch

VIEW ALL

VIEW ALL

Advertisement

Advertisement

LATEST

View More

Advertisement

Popular With Peers

More Oncology Studies

Latest Conferences

VIEW ALL

VIEW ALL

RELATED CONTENT

VIEW ALL

Sustained HRQOL in Patients With TGCT Over 2-Year Study

KEY TAKEAWAYS

  • The phase 4 trial aimed to assess HRQOL in patients with TGCT receiving pexidartinib treatment.
  • The study concluded that HRQOL remained stable in patients with TGCT during a 2-year follow-up, warranting further investigation.

Tenosynovial giant cell tumor (TGCT), a rare nonmalignant neoplasm affecting the synovium, bursae, or tendon sheath, typically emerges around age 40 and impacts health-related quality of life (HRQOL). Pexidartinib, the sole systemic therapy approved for adults with TGCT experiencing severe morbidity or functional limitations resistant to surgical intervention, has shown significant tumor response and enhanced functional outcomes since FDA approval in 2019.

Jayesh Desai and the team spearheaded a study that aimed to assess HRQOL in patients with TGCT receiving pexidartinib treatment, including discontinuation/rechallenge phases.

The study enrolled patients with TGCT from previous trials (NCT02371369; NCT01004861; NCT02734433; NCT03291288) following the previous trials’ end-of-treatment (EOT) visits.

Patients opted to either continue pexidartinib (Treatment Continuation Cohort [TCC]) at the same dose or discontinue treatment with the option to re-initiate (Treatment-Free/Re-Treatment Cohort [TF/RTC]) at the discretion of the investigator or patient. The change from Baseline in patient-reported outcomes (PROMIS physical function [PF], EQ-5D-5L) served as a secondary endpoint.

The results revealed that 32 patients participated in the study from October 2020 to April 2021 (21 in TCC, 11 in TF/RTC). These patients had a median age of 47.5 years (range: 21-81), a median of 7.8 years (4.6-32.6) from diagnosis to informed consent, and a median of 55.7 months (26.7-91.0) of prior pexidartinib treatment.

In the TCC group, the 24-month average paired change (APC) from Baseline was -2.78 (95% confidence interval: -6.20, 0.65) for PROMIS PF and -2.4 (-9.6, 4.8) for EQ-5D-5L VAS. During the TF period, the 24-month APC was -1.93 (-6.37, 2.51) for PROMIS PF and 3.4 (-3.6, 10.4) for EQ-5D-5L VAS. Of the 3 patients who re-initiated treatment, two experienced clinically significant (≥10 points) increases in PROMIS PF and EQ-5D-5L VAS.

The study concluded that despite prior reports of HRQOL decline in TGCT patients over time, HRQOL generally remained stable during the 2-year follow-up. Further investigations into HRQOL for patients receiving long-term continuous and intermittent pexidartinib treatment are warranted.

The trial was sponsored by the Daiichi Sankyo.

Source: https://www.ispor.org/heor-resources/presentations-database/presentation/intl2024-3895/139334

Clinical Trial: https://clinicaltrials.gov/study/NCT04526704

Desai J, Wagner AJ, Carrasco Garcia I et al. (2024). “Health-Related Quality of Life from a Phase 4 Global Clinical Study to Evaluate Discontinuation and Rechallenge of Pexidartinib in Patients with Tenosynovial Giant Cell Tumor (TGCT) Previously Treated with Pexidartinib.” Presented at ISPOR 2024, Atlanta, GA, USA, Value in Health, Volume 27, Issue 6, S1 (June 2024) (CO22).

Existential Experience in Cancer: Psilocybin Group Therapy

KEY TAKEAWAYS

  • The phase 2 trial aimed to investigate the impact of PAT on the existential experiences of patients coping with advanced cancer.
  • Researchers gained significant insights into PAT’s therapeutic mechanism and effects by exploring patients with cancer.

Advanced cancer poses an existential threat, raising for patients and caregivers the potential for both multi-dimensional suffering and growth. Despite its high prevalence among those with advanced cancer, existential distress remains insufficiently addressed by modern healthcare systems.

In response to this unmet need, psilocybin-assisted therapy (PAT) has emerged as a potential tool to address the existential needs of patients coping with advanced cancer. However, there is a lack of understanding regarding how patients articulate this aspect of their cancer journey and how it may be influenced by the mystical experiences induced by PAT, particularly within the context of group therapy.

Elise Tarbi and the team aimed to assess the full breadth of existential experiences described by patients with cancer during group PAT sessions.

They qualitatively analyzed existing data from semi-structured interviews with participants of the psilocybin trial, “The Safety and Efficacy of Psilocybin in Cancer Patients with Major Depressive Disorder” (NCT04593563). Among the 30 trial participants, 28 completed exit interviews. Using a qualitative descriptive approach paired with directed content analysis, an inclusive analysis was performed on interview transcripts, grounded in the Conceptual Model of Existential Experience in Adults with Advanced Cancer.

The analysis revealed 3 overarching themes that shed light on the existential journey of patients with cancer and depression during group PAT. Participants described a deepened lived understanding of their mortality, as well as a reckoning with and a re-prioritization of their attention, relationships, and efforts. Their therapeutic intentions for participating in the PAT trial went beyond relief of depression and extended to gain a new perspective towards existential worries – about death and dying and grief of actual or anticipated losses – and building spiritual resources to work toward desired states.

Lastly, they described the lasting effects of PAT as a healing transformation, noting an enhanced sense of meaning as well as new tools for coping with cancer and death anxiety, revitalized priorities and values, and deepened relationships with self and others.

The study concluded that by exploring the comprehensive descriptions of existential experiences among cancer patients during group Psilocybin-Assisted Therapy (PAT), valuable insights into the therapeutic mechanisms and effects of this emerging treatment modality were gained.

The trial was sponsored by Maryland Oncology Hematology, PA.

Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/14486

Clinical Trial: https://clinicaltrials.gov/study/NCT04593563

Tarbi E, Miner S, Nigam K, et al. (2024). “Descriptions of Existential Experience in Patients with Cancer and Major Depression Participating in Psilocybin-Assisted Group Therapy.” Presented at ONS 2024 (Abstract RS77).

Equitable Access for Disadvantaged Patients With PBT

KEY TAKEAWAYS

  • The trial aimed to explore the impact of area deprivation on symptom duration, treatment access, and survival in patients with PBTs.
  • The results showed that patients with PBT from socioeconomically disadvantaged areas face delays in accessing quality care, warranting future consideration.

Individuals living in areas of high deprivation, indicating socioeconomic disadvantage, often face challenges accessing treatment and experience higher mortality rates from cancer. However, little is known about how this deprivation affects the duration of symptoms, treatment accessibility, and survival among patients with primary brain tumors (PBTs).

Macy Stockdill and the team aimed to examine how area deprivation relates to the duration of symptoms before diagnosis, time to initial treatment, and overall survival among a cohort of 666 adults with PBTs participating in a substantial National Institutes of Health (NIH) observational trial.

The study utilized ordinal logistic regression to analyze the association between symptom duration (categorized as <6 months, 6 months-1 year, or ≥1 year) and area deprivation index (ADI) status (categorized as less advantaged or more advantaged), presenting ORs with 95% CIs.

Additionally, they employed linear regression to evaluate the relationship between time to treatment duration and ADI, providing beta coefficients along with 95% CIs. Adjustment for age at cancer diagnosis and gender (male or female) was made, with further stratification based on the residential distance to the National Institutes of Health (NIH) facilities (categorized as short distance, <200 miles, or long distance, 200+ miles).

Researchers subsequently employed Kaplan-Meier estimates to assess overall survival across different ADI levels based on residential distance. Furthermore, all models were stratified by tumor grade (low or high).

Among the 666 patients diagnosed with PBTs, 159 (24%) resided in less advantaged areas, while 40% lived long distances from treatment centers, and 24% had low-grade tumors. Individuals from less advantaged areas exhibited a higher 5-year survival rate compared to those from more advantaged areas (72.01% vs. 62.02%, P=0.02), although this difference was not significant when stratified by tumor grade (P=0.29 for low-grade tumors; P=0.09 for high-grade tumors).

The overall sample found no associations between ADI and symptom duration before diagnosis. However, time to any treatment was notably longer for all patients residing in less advantaged areas (β=7.78; 95% CI=0.02, 15.55), particularly among those with low-grade PBTs (β=36.19; 95% CI=12.17, 60.20).

Among individuals with low-grade PBTs living long distances from the NIH, the less advantaged group experienced a shorter duration of symptoms before diagnosis (OR=0.30; 95% CI=0.12, 0.75).

The study concluded that future consideration should be directed towards individuals diagnosed with PBTs who reside in socioeconomically disadvantaged areas, have low-grade PBTs, and live long distances from treatment centers. This demographic may encounter prolonged delays in accessing quality medical care on average.

The trial was sponsored by the National Cancer Institute (NCI).

Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/14915

Clinical Trial: https://clinicaltrials.gov/study/NCT02851706

Stockdill M, Vo JB, Kim Y, et al. (2024). “Impact of socioeconomic disadvantage on symptom duration, treatment initiation, and survival among primary brain tumor patients: A large cohort analysis.” Presented at ONS 2024 (RS76)

Overview of KCRS24: Annual Kidney Cancer Research Summit

Overview of KCRS24: Annual Kidney Cancer Research Summit

The Kidney Cancer Research Summit 2024 (KCRS24), which takes place July 11 to 12, promises to be a pivotal event in kidney cancer research. The summit, hosted by KidneyCAN and supported by leading institutions and sponsors, aims to spotlight cutting-edge advancements and foster collaborations among experts dedicated to combating renal cell carcinoma (RCC).

KCRS24: Keynote Address and Opening Sessions

The summit will be inaugurated with a welcome session by Bryan Lewis (KidneyCAN President) followed by a keynote address by Charles Swanton from The Francis Crick Institute, focusing on “How the Air We Breathe Can Impact Cancer.” The session will set the stage for exploring novel perspectives on environmental influences in cancer development.

Following this, Session 1 will delve into “Exploring Novel Drug Targets for RCC,” chaired by Pavlos Msaouel (MD Anderson Cancer Center) and Scott Tykodi (Fred Hutchinson Cancer Center).

Researchers from MD Anderson Cancer Center and Brigham & Women’s Hospital will present groundbreaking studies such as:

  • Purinergic receptor antagonist therapeutics presented by Jean Jiang (University of Texas Health San Antonio).
  • Novel therapeutic strategies for chromophobe RCC presented by Elizabeth Henske (Brigham & Women’s Hospital/Harvard Medical School).
  • Therapeutic relevance of targeting BCL-XL protein presented by Abhishek Chakraborty (Cleveland Clinic Foundation).
  • SETD2 deficiency in clear cell RCC presented by Neil Bhowmick (Cedars-Sinai Medical Center).

KCRS24: Innovations in Imaging and Biomarkers

Session 2, moderated by Eric Jonasch (MD Anderson Cancer Center) and Katy Beckermann (Vanderbilt University Medical Center), will shift focus to “Novel Imaging and Biomarkers to Guide RCC Patient Management.”

  • Xiankai Sun (University of Texas Southwestern Medical Center) will discuss advancements like PET imaging of HIF-2a.
  • Jeremiah Morrissey (Washington University in St. Louis) will talk about the multiplexed quantification of urinary biomarkers.
  • Christopher Weight (Cleveland Clinic Foundation) will delve into AI-based patient care strategies.

KCRS24: State of the Science and Diagnostic Advances

“State of the Science,” Session 3, chaired by Rohit Mehra (University of Michigan) and Payal Kapur (University of Texas Southwestern Medical Center), will explore the taxonomic evolution of kidney cancer, surgical pathology advancements, prognostic biomarkers, and updates on sarcomatoid RCC diagnosis and therapy.

Speakers will be Samson Fine (Memorial Sloan Kettering Cancer Center), Michelle Hirsch (Brigham & Women’s Hospital), Payal Kapur, Sabina Signoretti (Brigham and Women’s Hospital) and Rohit Mehra.

Trials in Progress and Future Directions

Session 4, moderated by Robert Motzer (Memorial Sloan Kettering Cancer Center) and Naomi Haas (Abramson Cancer Center/University of Pennsylvania), will focus on “Trials in Progress,” featuring updates on advanced RCC combination immunotherapy trials, novel drug studies like HC-7366 and Ubamatamab, and innovative approaches such as implantable microdevices for in vivo drug response evaluation. 

Speakers will be Michael Serzan (Dana-Farber Cancer Institute), Rana McKay (University of California, San Diego), Pavlos Msaouel (MD Anderson Cancer Center), Vincent Xu (Dana-Farber Cancer Institute), Toni Choueiri (Dana-Farber Cancer Institute) and Grant Stewart (University of Cambridge).

Clinical Updates and Immunotherapy Advances

Day 2 will commence with insights into “Obesity and Immunotherapy” by Jeffrey Rathmell (Vanderbilt University Medical Center), followed by Session 5 on “Clinical and Scientific Updates in Kidney Cancer,” moderated by Toni Choueiri.

This session will cover frontline systemic therapies, subsequent treatments for advanced disease, adjuvant options, and novel therapies beyond immunotherapy, providing a comprehensive update on therapeutic strategies across RCC stages and subtypes.

Speakers will be Thomas Powles (Barts Cancer Centre), Robert Motzer (Memorial Sloan Kettering Cancer Center), Bradley McGregor (Dana-Farber Cancer Institute), Laurence Albiges (Institut Gustave-Roussy), Rana McKay (University of California, San Diego) and David Braun (Yale Cancer Center).

Immunotherapy Advances and Emerging Research

Session 6, moderated by Hans Hammers (University of Texas Southwestern Medical Center) and David McDermott (Beth Israel Deaconness), will focus on “Immunotherapy Advances and Research.” Discussions will include the development of immunotherapy for kidney cancer, mechanisms of adoptive NK cell therapy, tumor-immune contexture in ccRCC, and novel targets like PTPN2/PTPN1 inhibitors and ex vivo models to predict immunotherapy responses.

Speakers will be Michael Atkins (Georgetown-Lombardi Comprehensive Cancer Center), Rizwan Romee (Dana-Farber Cancer Institute), Srinivas Malladi (University of Texas Southwestern Medical Center), Jonathan Powell (Calico Labs) and David Braun (Yale School of Medicine).

KCRS 24: Abstract Presentations and Future Directions

Session 7 will feature “Oral Abstract Presentations,” moderated by Rana McKay (University of California- San Diego) & Yuksel Urun (Ankara University School of Medicine).

  • The session will showcase the pivotal research on belzutifan versus everolimus, safety profiles of belzutifan monotherapy, CDK4/6 inhibition in RCC, and innovative approaches in liquid biopsy and gut microbiome modulation. 
  • These presentations will highlight emerging data crucial for shaping future treatment paradigms in kidney cancer.

Speakers will be Laurence Albiges (Institut Gustave-Roussy), Toni Choueiri (Dana-Farber Cancer Institute), Bradley McGregor (Dana-Farber Cancer Institute), Eddy Saad (Dana-Farber Cancer Institute), Karl Semaan (Dana-Farber Cancer Institute) and Nazli Dizman (MD Anderson Cancer Center).

Biotech Innovations and Therapeutic Prospects

The summit will end with Session 8, a “Biotech Showcase” moderated by Thomas Powles (Barts Cancer Centre) and Hans Hammers (University of Texas Southwestern Medical Center). 

Leading biotech companies will present their latest innovations, including Hif-2-alpha inhibitors, latent TGFβ1 inhibitors, α/β IL-2 receptor-biased partial agonists, bispecific antibodies, and novel cell therapies. 

Speakers will be Dimitry Nuyten (Arcus Biosciences), Lu Gan (Scholar Rock), Alex Azrilevich (Synthekine, Inc.), Chet Bohac (Xencor), Levi Gray-Rupp (ArsenalBio), Pavlos Msaeouel, (BostonGene, Principal Investigator), Kim Allman (Telix) and Natasha Lucero (Standard BioTools). 

KCRS 24: Research Highlights

KCRS 24: Conclusion and Awards

KCRS24 will conclude with awards recognizing innovation and excellence in kidney cancer research, including AACR-KidneyCAN grants and merit awards. This celebration of scientific achievements will highlight the collaborative efforts driving advancements in understanding, diagnosing, and treating kidney cancer.

KCRS24 promises to be a pivotal event catalyzing transformative breakthroughs in kidney cancer research. From exploring novel drug targets and biomarkers to advancing immunotherapy and biotechnological innovations, this summit serves as a beacon of hope for improving outcomes and quality of life for patients worldwide.

KCRS 2024: Sustaining Partners and Sponsors

Managing Post-Cilta-Cel CNP: Identification & Treatment

KEY TAKEAWAYS

  • The CARTITUDE phase 1,2 and 3 trials aimed to outline the incidence, presentation, and handling of CNP in patients treated with cilta-cel within CARTITUDE studies.
  • The results revealed that nurses need to recognize and treat CNP promptly, ruling out infection or myeloma progression as potential causes.

Treatment using the chimeric antigen receptor (CAR)-T cell therapy cilta-cel led to profound and enduring responses in relapsed/refractory multiple myeloma (RRMM) patients in CARTITUDE-1.

Additionally, in CARTITUDE-4, it demonstrated enhanced progression-free survival compared to standard-of-care in lenalidomide-refractory MM patients with 1 to 3 prior lines of therapy (HR, 0.26, P<0.0001). Neurotoxicities, such as cranial neuropathies (CNPs), have been reported in patients undergoing CAR-T cell therapies, highlighting the importance for nurses to be knowledgeable about their presentation and management.

Leslie Bennett and the team aimed to examine the occurrence, symptoms, and treatment of CNPs in patients treated with cilta-cel within CARTITUDE trials.

In the CARTITUDE studies (CARTITUDE-1, CARTITUDE-2 – cohorts A, B, and C, and CARTITUDE-4), patients were administered cilta-cel via infusion. CNP were graded using the NCI-CTC Adverse Event reporting guidelines. A typical diagnostic evaluation for CNP cases involved cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) at the investigator’s discretion.

The results revealed that CNPs were observed in 21 out of 332 (6.3%) patients treated with cilta-cel. The median time to symptom onset was 22 days (range: 17-101 days), with 81% occurring around day 22 ± 5. Predominantly male patients (81%) experienced CNPs, mostly presenting as grade 2 cases; however, 3 patients had grade 3 CNP. Cranial nerve (CN) VII was involved in all cases, with 2 cases additionally involving CN V (both grade 3) and 1 involving CN III (grade 3). CNPs were noted to be bilateral in six cases and unilateral, predominantly left-sided, in 15 cases.

About 12 patients experienced simultaneous neurological symptoms or other neurotoxicities, 1 patient had prior grade 2 immune effector cell–associated neurotoxicity syndrome (ICANS), and no patients with CNP exhibited movement or neurocognitive toxicity, such as parkinsonism.

No evidence of infectious or malignant etiology was found through cerebrospinal fluid (CSF) analysis (n=14) or brain MRI (n=17), although facial nerve enhancement was observed in seven MRI cases. Treatment for CNP included corticosteroids, with a median duration of 13 days. CNP resolved in 19 out of 21 patients, even in grade 3 cases, with a median resolution duration of 66 days.

The study concluded that following cilta-cel treatment in the CARTITUDE program, CNP predominantly presented as low grade and typically resolved with a short course of corticosteroid treatment in the majority of patients.

The incidence of CNP was not correlated with prior grade ≥2 cytokine release syndrome (CRS) or any-grade ICANS. Nurses must be adept at identifying and treating CNP, including conducting a comprehensive differential diagnosis to eliminate infection or myeloma disease progression as potential causes.

The trial was sponsored by the Janssen Research & Development, LLC.

Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/15574

Clinical Trials: https://clinicaltrials.gov/study/NCT03548207
https://clinicaltrials.gov/study/NCT04133636
https://clinicaltrials.gov/study/NCT04181827

Bennett L, Kruyswijk S, Sidana S, et al. (2024). “Incidence and Management of Cranial Nerve Impairments in Patients With Multiple Myeloma Treated With Ciltacabtagene Autoleucel in CARTITUDE Studies.” Presented at ONS 2024 (I21)

Managing Dermatologic Toxicities With Talquetamab in R/R MM

KEY TAKEAWAYS

  • The MonumenTAL-1 phase 1 & 2 trial aimed to investigate the management considerations for dermatologic toxicities associated with talquetamab in patients with R/R MM.
  • Researchers noticed that proper management of GPRC5D-related dermatologic toxicities enhances patient adherence to talquetamab, optimizing treatment benefits.

Talquetamab is an FDA-approved T-cell redirecting bispecific antibody targeting the G protein-coupled receptor class C group 5 member D (GPRC5D) on myeloma cells. The MonumenTAL-1 study demonstrated >71% overall response rates (ORR) in patients with relapsed/refractory multiple myeloma (RRMM). GPRC5D-related adverse events (AE), notably dermatologic toxicities, present as on-target, off-tumor effects necessitating additional supportive care.

Elaine Esler and the team aimed to assess the management considerations for dermatologic toxicities associated with talquetamab in RRMM patients.

They performed an inclusive analysis of MonumenTAL-1, an open-label, single-arm, phase 1/2 study in patients with RRMM. The study evaluated the recommended phase 2 doses (RP2Ds) of subcutaneous talquetamab at 0.4 mg/kg weekly and 0.8 mg/kg every other week.

About 339 patients, including those with prior T-cell redirection therapies, received subcutaneous talquetamab at the RP2Ds. Dermatologic toxicities encompassed rash, non–Rash–related skin issues, and nail toxicities, occurring in 34.8%, 65.2%, and 55.5% of patients, respectively. Most of these toxicities were low-grade (rash, 3.5% grade 3; non–rash–related, 0.3% grade 3).

Median onset times ranged from 20–27 days for rash, 26–30 days for non–Rash–related skin, and 64–69 days for nail toxicities, with durations spanning 15–28, 32–39, and 74–122 days, respectively. Resolution rates were 78.9% for rashes, 59.4% for non–rash–related skin, and 29.5% for nail toxicities. No treatment discontinuations resulted from rash or nail toxicities, and 0.9% due to non–rash–related skin toxicities.

The study concluded that proper management strategies, including patient education and supportive care, significantly contribute to the low rates of dermatologic AE-related discontinuation in talquetamab treatment. Nurses counsel patients on skincare practices such as maintaining skin hygiene, using moisturizers, and staying hydrated.

Specific guidance on nail care, including avoiding activities that may damage nails and wearing protective gloves or socks, is recommended. Monitoring for secondary skin infections is essential. Early intervention with corticosteroids and emollients, such as ammonium lactate cream, aids in managing skin and nail toxicities effectively.

Overall, comprehensive management addressing GPRC5D-related skin and nail toxicities ensures patient adherence to treatment and maximizes the therapeutic benefits of talquetamab.

The trial was sponsored by Janssen Research & Development, LLC.

Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/15521

Clinical Trials: https://clinicaltrials.gov/study/NCT03399799

https://clinicaltrials.gov/study/NCT04634552

Esler E, Gray K, Hefner K, et al. (2024). “Management Considerations for Dermatologic Toxicities Associated With Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma.” Presented at ONS 2024 (Abstract I24).

AVA6000: Targeted Doxorubicin Delivery for Antitumor Activity

KEY TAKEAWAYS

  • The phase 1 trial aimed to investigate the efficacy and safety of AVA6000 in patients with FAP-positive solid tumors, focusing on targeted delivery and therapeutic outcomes.
  • Researchers noticed significant antitumor activity in FAP-positive tumors due to high doxorubicin concentrations in the TME, which supports AVA6000 efficacy.

AVA6000 is a peptide drug conjugate designed for targeted delivery of doxorubicin to solid tumors with high fibroblast activation protein (FAP) activity in the tumor microenvironment (TME). FAP, overexpressed in many solid tumors, cleaves the peptide moiety of AVA6000, releasing doxorubicin specifically within the TME. The peptide moiety linker, Pre|CISIONTM, prevents cellular entry of doxorubicin until cleaved by FAP, enhancing tumor specificity.

U. Banerji and the team aimed to assess the efficacy and safety of AVA6000 in FAP-positive solid tumors. Preliminary results indicated promising antitumor activity and support ongoing dose escalation studies to further evaluate its potential in clinical settings.

They performed an inclusive analysis of the safety, pharmacokinetics (PK), and preliminary efficacy of AVA6000 in a first-in-man, multicenter dose-escalation phase I trial. AVA6000 was administered intravenously every 3 weeks using a standard 3+3 design in patients with locally advanced or metastatic solid tumors reported to be FAP-positive. PK-based dosing, utilizing area under the curve (AUC), was implemented to calculate maximum cycles of AVA6000, with a cumulative limit of 550 mg/m2.

About 40 patients (median age 65 years, range 30-79) receiving a median of 3 prior lines of therapy (range 0-7) were administered escalating doses of AVA6000 in a multicenter dose-escalation phase I trial. The doses ranged from 80 mg/m2 (equivalent to 51 mg/m2 of doxorubicin) to 385 mg/m2 (equivalent to 260 mg/m2 of doxorubicin). Patients presented with various tumor types, including soft tissue sarcoma (30%), colorectal cancer (27.5%), pancreatic cancer (20%), and cancers of the biliary tract (7.5%).

Overall, the safety profile of AVA6000 was favorable, with the most frequent adverse events (any grade) reported as fatigue (50%), alopecia (42.5%), and nausea (32.5%). Grade 3-4 hematologic toxicities were infrequent, with neutropenia, anemia, thrombocytopenia, and decreased white blood cell (WBC) count occurring in 5% of patients. Grade 3 non-hematologic toxicities included mucositis, fatigue, and hematemesis, each observed in 1 patient.

Two dose-limiting toxicities were reported, which were one case of grade 2 cardiac failure at a dose of 120 mg/m2 (with a decrease in left ventricular ejection fraction from 61 to 39%) and one case of grade 4 neutropenia/thrombocytopenia at a dose of 200 mg/m2. AVA6000 exhibited rapid distribution, with a half-life of 45 minutes. The maximum concentration (Cmax) of released doxorubicin was reduced compared to standard dose doxorubicin across dose cohorts, with a range of 78-93% reduction.

Tumor biopsy data demonstrated a mean concentration of doxorubicin in the TME of 860 ng/gm (range 76-2310 ng/gm, n=9). In contrast, blood samples collected at the biopsy showed a circulating free doxorubicin concentration of 8.3 ng/ml (range 2.4-15.9), indicating a higher concentration of doxorubicin in the tumor relative to plasma.

Using RECISTv.1.1 criteria, 1 patient achieved a partial response (-65%) lasting 6 months in undifferentiated pleomorphic sarcoma at a dose of 160 mg/m2, and another patient exhibited a mixed response (SLD -22%) in angiosarcoma at a dose of 200 mg/m2. The disease control rate at 12 weeks was 50%, with SD>4 months or partial response observed in 6 patients. Notably, high FAP enzyme activity in on-study tumor biopsies correlated with stable disease or partial response in these cases.

The study concluded that AVA6000 effectively delivers a high concentration of doxorubicin to the TME relative to plasma, leading to significant antitumor activity in tumors with high FAP activity. Ongoing dose escalation arms every 2 weeks (q2w) further investigate its potential.

The trial was sponsored by Avacta Life Sciences Ltd.

Source: https://www.abstractsonline.com/pp8/#!/20272/presentation/11478

Clinical Trial: https://clinicaltrials.gov/study/NCT04969835

Banerji U., Cook N., Anthoney A., et al. (2024). “A Phase I trial of AVA6000, a Fibroblast Activation Protein (FAP)-released and tumor microenvironment (TME)-targeted doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors.” Presented at AACR 2024 (Abstract CT188 / 16).

VIEW ALL

SELECT ONCOLOGY JOURNAL ARTICLES

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab

Background We have previously published initial efficacy of the indoleamine 2,3-dioxygenase (IDO)/anti-programmed death ligand 1 (PD-L1) vaccine in combination with nivolumab in 30 anti-PD-1 therapy naïve patients with metastatic melanoma (cohort A). We now report long-term …

BMJ Journals

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)

Background To determine the efficacy and toxicity of nivolumab monotherapy in treatment-naïve patients with non-clear cell renal cell carcinoma (nccRCC) and the efficacy of nivolumab/ipilimumab salvage therapy in patients with tumors unresponsive to initial nivolumab monotherapy. Methods Eligible …

BMJ Journals

Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4+ naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma

Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4+ naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma

Background Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, …

BMJ Journals

1222 Antigen-specific delivery of TCR and costimulatory signals by a protein scaffold selectively activates and markedly expands naïve MART-1-specific CD8+ T cells

1222 Antigen-specific delivery of TCR and costimulatory signals by a protein scaffold selectively activates and markedly expands naïve MART-1-specific CD8+ T cells

Background Adoptive cell transfer (ACT) shows promise as an immunotherapy for melanoma and other cancers. However, there are several challenges associated with ACT such as the logistical complexity and inconsistency when using patient-derived antigen-presenting cells for …

BMJ Journals