Last Updated: 12/13/2024

STAFF HIGHLIGHT: Richard Little, MD

How have the therapeutic options for hematologic and AIDS-related cancers and hematopoietic stem cell transplants changed since you joined NCI?

There has been remarkable progress since I joined NCI in 1992. Early therapeutics for HIV were single-agent, antiretroviral reverse transcriptase inhibitors that were temporizing at best, stabilized the inexorable march of HIV for a few months, and led to death in nearly every patient. The disease was often complicated by aggressive lymphomas or Kaposi sarcoma. Since the early 1990s, the incidence of these cancers has greatly decreased, and we can now effectively treat Kaposi sarcoma and AIDS-related lymphomas. Advances in antiretroviral therapy allow patients with HIV infection to have a near normal lifespan compared to the background population. For stem cell transplants, various donor sources can be used now, so almost everyone can access that modality if it is indicated in the treatment of their underlying hematopoietic disease. Also, we know that individuals with HIV infection benefit in the same way with both auto-transplantation and allo-transplantation.

We’ve also seen astounding advances in leukemias and multiple myeloma through NCI-sponsored clinical trials conducted through the NCI National Clinical Trials Network (NCTN). Trials in chronic lymphocytic leukemia (CLL) have investigated ibrutinib, which is effective and given instead of multimodality toxic chemotherapy. Now the focus is to research ways to abbreviate treatment instead of requiring it for many years. In acute lymphoblastic leukemia (ALL), particularly B cell, the advances are remarkable. ECOG-ACRIN led a study showing that blinatumomab improved survival substantially for minimal residual disease (MRD)-negative ALL in adults (Litzow, 2024).

For acute myeloid leukemia (AML), we are learning that driver mutations can be targeted with specific therapies. We have embarked on a precision medicine initiative for AML and myelodysplastic syndromes (MDS), myeloMATCH, which we hope will change the treatment paradigm. The trial recently opened, and it is starting to enroll patients.

What makes the design of myeloMATCH unique?

We will enroll newly diagnosed patients with AML or MDS, use rapid genomic testing to identify the genomic abnormalities in their cancer, and assign them to experimental therapeutics. Patients will be assigned to an initial tier of therapy, which is equivalent to induction or their first therapy. After their first therapy, patients can be reevaluated and assigned to a higher tier of therapy that would be equivalent to consolidation or transplant. The various NCTN groups lead each of these trials.

Each patient will be assigned an identification number that follows them throughout their treatment journey while enrolled on the trial. As patients are assigned to different protocols, we will easily connect them and their specimens using advanced assays for MRD. This approach will help us understand clonality and treatment effects because we can easily retrieve data to know which patients, protocols, treatments, and genomic findings line up. This will be an incredible database for our investigators to use to understand treatment sensitivity and resistance in these diseases.

Do you think other groups will adopt this trial design?

myeloMATCH is complicated and took more than five years to develop before the recent launch. It is designed to answer the question: Can we approach diseases and study them in this efficient and effective way? We hope to learn a lot and leverage the NCTN in a way that will be incredibly effective in advancing therapeutics. Before this design can be used to study other diseases, we need the data from this trial to understand how well it works within the NCTN system.

How has patient eligibility metrics changed since you joined NCI and what spurred your efforts to expand eligibility criteria?

Clinical trials have changed since I came here, including their design, conception, and review. When writing new protocols, clinical investigators cut and pasted text, particularly eligibility criteria and laboratory and radiographic assessments, from protocols of previous trials. In the 1990’s and early 2000s, I remember attending in the NIH Clinical Center and discussing cases and protocols with other fellows - universally, people with HIV were excluded from trials. In the early days of HIV that made sense because the disease was not controlled and was its own special oncologic issue. When good antiretroviral therapy came along, the reflexive exclusion no longer made sense. In 2008, Christine Grady, Gorvind Persad, and I published a paper (Persad, 2008) that examined the medical and ethical rationale for continuing or not continuing the exclusion of individuals with HIV. I also just moved from the NIH Clinical Center to CTEP, and we started including individuals with HIV infection in clinical trials. Around 2005-2007, the American Society of Clinical Oncology and Friends of Cancer Research developed committees to assess eligibility criteria in terms of different comorbid conditions, including HIV, heart disease, and prior cancers. They produced recommendations, and CTEP developed ways to implement them. Many of us at CTEP served on those committees and participated in developing the recommendations.

The implementation was more difficult than the formulation of the recommendations because people were used to just cutting and pasting from previous protocols. We saw that many investigators did not adhere to the recommendations, or some company collaborators asked for changes in the protocols after they were written. These observations led us to develop a pilot project in 2021 focused on broadening eligibility in CTEP-supported protocols. In this project, a group of dedicated CTEP staff reviewed each protocol and revision to ensure that the new eligibility criteria were either in the protocol and stayed there through all the revisions, or there was a valid medical or scientific reason not to broaden a particular eligibility criterion. Clinical trials need to be representative of the people who get the diseases. Some minority communities may have an excess representation of a particular comorbid condition, and without safely broadening those criteria, we inadvertently make it more difficult for certain communities to be eligible for a clinical trial.

Is NCI on the forefront of expanding eligibility criteria?

The work that we did in HIV, showing that auto-transplants and allogeneic transplants are safe and effective in individuals with HIV infection, laid the groundwork to demonstrate that intensive toxic therapy can be safe. Our experience enrolling people with HIV, hepatic dysfunction, and performance status of 2 instead of 1, helped skeptical people to become more comfortable enrolling these patients.

What about expanding clinical trial eligibility for older-aged people?

It’s important to understand the relevant clinical question for an older patient, which may differ compared to younger patients or may be disease specific. In CLL, we began investigating ibrutinib, which has become the new standard of care. We decided to have separate trials for younger and older patients due to different standards of care and accrual rates. Combining the two populations would have been operationally difficult and statistically challenging. The two separate trials were very effective - both accrued ahead of schedule, met their primary endpoints, and established a new standard of care.

What do you enjoy most about working at NCI?

I enjoy the fantastic camaraderie amongst the very smart people who work at NCI. You learn so much every day from colleagues here. It is an incredible privilege and opportunity to be around people who care about what they're doing, who share the same mission, and who work together for important goals.

What challenges remain for hematological trials and what steps can be taken to overcome these challenges?

Despite the rapidly moving science in terms of new agents that can be tested therapeutically, the most important challenge is to prioritize and develop the science in a logical way before launching definitive trials. We need to avoid wasting time on negative phase 3 studies and ensure that when phase 3 studies are launched, we have good supporting data. We need to ensure that when patients give their time to participate in a trial, we have developed a study in the most potentially productive way.

SPOTLIGHT: NCI Is Accepting Reagent Target Requests to the NCI Antibody Characterization Program from November 1, 2024 — February 14, 2025

To accelerate biomarker discovery and validation, cancer diagnostics development, and therapeutics monitoring, DCTD’s Antibody Characterization Program announced the next target request submission period. Interested researchers with readily available protein/peptides can submit a request using the cancer reagent target requests form. Requests will be reviewed and considered for merit based on their justification and contribution to existing NCI-funded projects.

The submission period is from November 1, 2024 — February 14, 2025, and target selection notification will be on or before April 15, 2025.

SPOTLIGHT: New NCI National Clinical Trials Network (NCTN) Biospecimen Catalog Provides Expanded Access to Biospecimen Information

The NCTN Biobanks are an integral part of the NCTN and a central resource for the collection, processing, and storage of biospecimens from NCTN phase 3 and phase 2 trials. They are a valuable resource for well-annotated biospecimens and have associated clinical and outcome data that are used for research aims and objectives to advance cancer treatment.

The NCTN Biobanks provide access to well-annotated legacy biospecimens for all researchers for other secondary studies. To facilitate this, DCTD developed a comprehensive and searchable resource, the NCTN Biospecimen Catalog, which provides detailed listings of clinical trial biospecimens available across all NCTN Biobanks for secondary use.

This catalog includes biospecimens from NCTN trials that are in the NCTN Navigator system , as well as other available biospecimens from NCTN trials that are not in NCTN Navigator. The catalog search results guide investigators to the appropriate resource for submitting requests for specific biospecimens, to NCTN Navigator for the trials uploaded there, or directly to the relevant NCTN Group Biobanks for trials not yet in NCTN Navigator.

NEWS ACROSS DCTD

myeloMATCH Will Test Tailored Treatments for AML and MDS

Excerpt from the NCI press release:

The National Institutes of Health (NIH) has launched a proof-of-concept precision medicine clinical trial to test new treatment combinations targeting specific genetic changes in the cancer cells of people with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The trial, funded by NIH’s National Cancer Institute (NCI), aims to accelerate the discovery of more tailored treatments for these aggressive cancers of the blood and bone marrow. The precision medicine trial aims to match patients to treatments based on the genetics of their cancer.

Initially, people enrolled in the trial with newly diagnosed AML or MDS will undergo rapid genetic testing of their tumor samples. Based on the molecular characteristics of their tumors, they will be matched to a substudy testing a treatment appropriate for the specific genetic changes and characteristics associated with their disease, if one is available, or to standard treatment if an appropriate substudy is not available.

If the initial treatment works to reduce a patient’s disease, they will undergo further genetic testing to match them to a subsequent substudy testing a treatment that is appropriate for the specific genetic changes associated with their remaining disease. As the amount of a patient’s disease decreases, study investigators will use increasingly sensitive tools, such as biomarker assays, to identify appropriate treatments for any remaining cancer cells.

Read more about myeloMATCH.

Investigators Are Invited to Contribute Data to the NCI Integrated Canine Data Commons (ICDC)

DCTD invites comparative oncology investigators and veterinary oncologists working with pet dogs that develop spontaneous cancers to contribute annotated data to the ICDC.

Established as a cloud-based data repository node within the Cancer Research Data Commons (CRDC), the ICDC permits scientists to explore, analyze, and understand the biological relationships between human and canine cancers. The ICDC is accessible to the scientific community without charge. Learn more about comparative oncology at NCI and how to contribute data.

In Vivo Engineering of Immune Cells (IVEIC) for Cancer Immunotherapy Workshop — January 28-29, 2025

NCI is convening a virtual workshop on January 28 and 29, 2025 on “In Vivo Engineering of Immune Cells (IVEIC) for Cancer Immunotherapy.”

The workshop aims to spur discussion of the IVEIC approach, which reprograms specific immune cells inside the body, and foster collaboration among investigators from multidisciplinary fields of immuno-oncology, gene and cell engineering, and nanomaterials.

Sessions will include discussions of:

• Viral and synthetic-based gene delivery to generate CAR T cells in situ
• Precision genome editing technologies for immune cell reprogramming
• In vivo cell engineering beyond CAR T cells
• Clinical perspectives of the IVEIC approach

Registration and more information.

Inside Cancer Careers Podcast Features Dr. Christophe Marchand

In Season 2-Episode 16: Staff Scientists: The Swiss Army Knife of NCI, of Inside Cancer Careers, Dr. Swati Choksi, a Staff Scientist at NCI Center for Cancer Research, and Dr. Christophe Marchand, Deputy Associate Director in DCTD and former Staff Scientist, share insights about their roles in cancer research. They podcast focuses on:

• Advantages and responsibilities of being a staff scientist, such as mentoring and training early career researchers and conducting their own experiments
• Importance of staff scientists in fostering collaborations within and outside the research team
• Transferability of skills, potential career paths for staff scientists, and more

Radiation Research Program Staff Contribute to Foundations for Digital Twins as Catalyzers of Biomedical Technological Innovation Program

The National Science Foundation (NSF), NIH, and FDA are supporting seven projects that are exploring digital twin technology for biomedical applications. Researchers will explore the potential of digital twin technology to be used in the future for virtual clinical trials of cardiovascular medical devices, understanding neurodegenerative diseases, and more. For more information on this effort, contact Dr. Jeff Buchsbaum (jeff.buchsbaum@nih.gov).

Read NSF’s press release.

President Biden’s Cancer Cabinet Community Conversations

Federal agencies and departments that are part of the Cancer Cabinet hosted a series of virtual roundtable discussions to inform and advance Cancer Moonshot priorities. Dr. Radim Moravec, CTEP, was a panelist in this event and discussed NCI’s Virtual Clinical Trials Office pilot program. Watch a recording of the July 2024 virtual event.

Selected Staff Publications

• Prasanna P. Harnessing senescence for antitumor immunity to advance cancer treatment. Rad Res. 2024 Nov 1;202(5):723-733.
  PubMed

• As part of a Friends of Cancer Research (Friends) Homologous Recombination Deficiency (HRD) Working Group, DCTD staff co-authored a publication in the Journal of Clinical Oncology Advances (Andrews HS, 2024 ) that examines variability in outputs from HRD assays assessing a common sample set. HRD is a biomarker used to determine eligibility for Poly ADP-ribose Polymerase Inhibitors to treat patients with high-grade serous ovarian carcinoma. The findings demonstrate variability in HRD results across assays, suggesting the need for consistent and aligned strategies in biomarker selection for clinical trials and clinical decision-making in oncology drug development.

  Excerpt from the Friends press release: “While the analysis set the groundwork for what needs to occur to create alignment, we did not focus on a gold standard due to a lack of agreement on what that might be,” said Dr. Lisa McShane Associate Director, Division of Cancer Treatment and Diagnosis at the National Cancer Institute. “For all diagnostic development, it is important that gold standards and reference datasets are established to improve assay output consistency.”

• Prasanna PGS, Ahmed MM, Hong JA, and Coleman CN. Best practices and novel approaches for the preclinical development of drug-radiotherapy combinations for cancer treatment. Lancet Oncol. 2024 Oct;25(10):e501-e511.
  PubMed
• Smith MA, Houghton PJ, Lock RB, et al. Lessons learned from 20 years of preclinical testing in pediatric cancers. Pharmacol Ther. 2024 Nov 5;264:108742.
  PubMed

• NCI staff convened a workshop on uterine serous cancer (USC) in June 2023 to spur interest in research, identify knowledge gaps, and discuss the marked health disparities seen in USC. USC accounts for about 10% of all endometrial cancer (EC) cases but causes 40% of EC deaths.

  Staff prepared a workshop report and identified some opportunities for action:

  • Focusing scientific directions
  • Expanding, enhancing, and optimizing the use of models, biospecimens, and data resources
  • Fostering development of the scientific community

  Read the full report.

• Dexheimer TS, Coussens NP, Silvers T, et al. Combination screen in multi-cell type tumor spheroids reveals interaction between aryl hydrocarbon receptor antagonists and E1 ubiquitin-activating enzyme inhibitor. SLAS Discov. 2024 Oct;29(7):100186.
  PubMed

• A SWOG and NCI National Clinical Trials Network collaborative, randomized phase 3 trial (S1826) assessed patients with stage 3 or 4 newly diagnosed Hodgkin’s lymphoma. Adult and adolescent and young adult patients 12 years and older who received the immunotherapy nivolumab (N) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) had longer progression-free survival compared to patients who received brentuximab vedotin (BV)+AVD.

  Fewer patients on the N+AVD regimen stopped treatment early and showed a lower incidence of immune-related toxic effects and fewer deaths compared to those on the BV+AVD regimen. Radiotherapy was not necessary for the adolescent and young adult patients.

  Read the publication.

• Prindiville SA, Mandrekar SJ, Meropol NJ, et al. Streamlining the Conduct of Cancer Clinical Trials: New Standard Data Collection Practices for National Cancer Institute Late Phase Clinical Studies. J Natl Cancer Inst. 2024 Sep 26:djae239.
  PubMed

• DCTD staff coauthored a report on the NCI workshop titled “Circulating Tumor DNA (ctDNA) in Cancer Treatment and Clinical Care,” which convened on September 14-15, 2023. The goal of the meeting was to discuss the landscape and requirements for the future of ctDNA in the treatment and management of solid tumors, and how the scientific community can best assess the value of ctDNA technology.

  The authors reflected on using ctDNA as a proposed tool for effective treatment monitoring and its distinctive predictive and prognostic capabilities.
  Read the full report.

• NCI staff from DCTD, the Division of Cancer Prevention, Division of Cancer Biology, and Division of Cancer Control and Population Sciences coauthored a report on the older American population based on the 2023 webinar series “Cancer, Aging, and Comorbidities.” The older American population with cancer is more likely to have comorbidities and experience specific challenges in their cancer treatment than younger patients.

  A few opportunities for action identified in the paper were to discover and validate biomarkers and targets to better predict and intervene treatment-related toxicity in a personalized manner for this specific population and to design cancer clinical trials specific for the older population to generate data to support evidence-based treatment decision making.

  Read the full report.

NCI-COG Pediatric MATCH Publications

Vo KT, Sabnis AJ, Williams PM, et al. Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial. JCO Precis Oncol. 2024 Jun;8:e2400103.
PubMed

Macy ME, Mody R, Reid JM, et al. Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I). JCO Precis Oncol. 2024 Sep;8:e2400418.
PubMed

Laetsch TW, Ludwig K, Williams PM, et al. Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D. JCO Precis Oncol. 2024 Sep;8:e2400258.
PubMed

Glade Bender JL, Pinkney K, Williams PM, et al. Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial. Oncologist. 2024 Jul 5;29(7):638-e952.
PubMed

Nelson MV, Kim A, Williams PM, et al. Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G. Oncologist. 2024 Aug 5;29(8):723-e1093.
PubMed

FUNDING UPDATES

Title	Announcement Number	Closing Date	Activity Code
NCI National Clinical Trials Network	RFA-CA-24-030 Companion Notices: RFA-CA-24-031 RFA-CA-24-032 RFA-CA-24-033 RFA-CA-24-034 RFA-CA-24-035	February 25, 2025	U10
Innovative Research in Cancer Nanotechnology (IRCN; Clinical Trial Not Allowed)	PAR-25-106	April 5, 2025	R01
Cancer Tissue Engineering Collaborative: Enabling Biomimetic Tissue-Engineered Technologies for Cancer Research (Clinical Trial Not Optional)	PAR-25-171	May 8, 2025	R01
Systematic Testing of Radionuclides in Preclinical Experiments (STRIPE) (Clinical Trial Not Allowed)	PA-25-174	May 8, 2025	R01
Microbial-based Cancer Imaging and Therapy — Bugs as Drugs (Clinical Trial Not Allowed)	PAR-25-108	May 8, 2025	R21
Microbial-based Cancer Imaging and Therapy — Bugs as Drugs (Clinical Trial Not Allowed)	PAR-25-107	May 8, 2025	R01
Systematic Testing of Radionuclides in Preclinical Experiments (STRIPE) (Clinical Trial Not Allowed)	PA-25-173	May 8, 2025	R21
NCI Clinical and Translational Exploratory/Development Studies	PAR-25-139	July 2, 2025	R21
Co-infection and Cancer (Clinical Trial Not Allowed)	PAR-25-083	January 8, 2026	R21
Assay Development and Screening for Discovery of Chemical Probes, Drugs, or Immunomodulators (Clinical Trial Not Allowed)	PAR-25-153	September 8, 2026	R01
Assay Validation of High Quality Markers for Clinical Studies in Cancer (Clinical Trial Not Allowed)	PAR-25-074	October 15, 2026	UH2/UH3
Assay Validation of High Quality Markers for Clinical Studies in Cancer (Clinical Trial Not Allowed)	PAR-25-075	October 15, 2026	UH2/UH3
Revision Applications for Validation of Biomarker Assays Developed Through NIH-Supported Research Grants (Clinical Trial Not Allowed)	PAR-24-304	October 15, 2026	R01
National Cancer Institute’s Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (Clinical Trial Required)	PAR-25-081	January 8, 2027	R01
Academic-Industrial Partnerships (AIP) to Translate and Validate In Vivo Imaging Systems (Clinical Trial Optional)	PAR-25-079	January 8, 2027	R01
Bioengineering Partnerships with Industry (Clinical Trial Optional)	PAR-24-325	September 8, 2027	U01
Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (Clinical Trial Optional)	PAR-25-175	January 8, 2028	R01
Molecular Imaging of Inflammation in Cancer (Clinical Trial Not Allowed)	PAR-24-311	January 8, 2028	R01

CAREERS

DCTD would like to fill several positions, including but not limited to, the following:

• Clinical Fellow/Senior Clinical Fellow for the Advanced Developmental Therapeutics Training Program in the Developmental Therapeutics Clinic
• Associate Director, Cancer Imaging Program
• Associate Director, Radiation Research Program
• Branch Chief, Biological Testing Branch, Developmental Therapeutics Program
• Pharmacologist, Toxicology and Pharmacology Branch, Developmental Therapeutics Program

See the full list of available positions, descriptions, and contact information.