Anti-CD38 + KRAS Vaccine + Anti-PD-1 for Pancreatic & Lung Cancer

(DARANIVOVAX Trial)

Recruiting at 2 trial locations

Overseen By Benjamin A. Weinberg

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Anti-CD38 therapies, Live vaccines

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 8

Duration: approximately 2 years

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating advanced lung and pancreatic cancers by combining three therapies: daratumumab (an anti-CD38 antibody), a KRAS vaccine, and nivolumab (an anti-PD-1 therapy). The main goal is to determine if this combination can better control or stop these cancers, assess patient tolerance, and potentially extend survival. This trial may suit individuals with advanced non-small cell lung cancer that worsened after initial treatment or pancreatic cancer unresponsive to one prior treatment. Participants will undergo regular tests to monitor their response to these treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for some treatments, such as a 1-week washout for certain targeted therapies and a 4-week washout for anti-PD-1/PD-L1 therapies. It's best to discuss your current medications with the trial team to understand any specific requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that daratumumab, a lab-made protein that attaches to substances in the body, is generally well tolerated. Although some serious side effects have been reported with other treatments, they are uncommon.

Studies indicate that the KRAS vaccine has a good safety record, typically causing few serious side effects. It aids the immune system in fighting cancer cells.

Nivolumab, another lab-made protein, has been used successfully to treat lung cancer and tends to have fewer side effects than other chemotherapy drugs. While some patients experience serious side effects, these are rare.

Overall, these treatments have been used in various situations and have generally been safe, with some risks, as is common with cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of daratumumab, a KRAS vaccine, and nivolumab for pancreatic and lung cancers because these treatments target cancer in a novel way. Most current treatments focus on chemotherapy and radiation, but this combination harnesses the immune system to attack cancer cells. Daratumumab targets CD38 proteins on cancer cells, the KRAS vaccine stimulates an immune response against a common cancer mutation, and nivolumab blocks a protein called PD-1, which tumors use to hide from the immune system. This multi-faceted approach not only aims to be more effective but might also lead to fewer side effects compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for pancreatic and lung cancer?

This trial will examine the effects of combining different treatments for pancreatic and lung cancers. Daratumumab, a monoclonal antibody, is being tested for its potential use in these cancers by helping the immune system attack cancer cells. The KRAS vaccine, another treatment option in this trial, may strengthen the body's defense against pancreatic cancer, which often involves changes in the KRAS gene. For lung cancer, early studies showed positive results with treatments targeting KRAS. Nivolumab, also included in this trial, is a monoclonal antibody that has extended the lives of patients with advanced non-small cell lung cancer and shows promise when combined with chemotherapy for pancreatic cancer. Overall, this trial studies these treatments for their ability to stop or slow cancer growth. ^{2 6 7 8 9}

Who Is on the Research Team?

Samir Khleif, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer or pancreatic ductal adenocarcinoma that's worsened despite treatment. Participants must have specific KRAS mutations, acceptable organ function, and no other recent cancers or severe illnesses. They can't be pregnant/nursing and must agree to use contraception.

Inclusion Criteria

Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

I am willing to give tissue samples for research.

My advanced lung cancer is getting worse despite initial treatment, but it's not rapidly progressing.

Exclusion Criteria

You have a mental illness or social situation that would make it hard for you to follow the study rules.

You have had serious allergic reactions to certain types of medications or vaccines in the past.

You have a history of autoimmune disease or are at risk of developing one.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, nivolumab with KRAS vaccine and have regular tests and procedures

approximately 2 years

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days following discontinuation of intervention

Long-term Follow-up

Participants are monitored for overall survival and duration of response

approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• KRAS vaccine
• Nivolumab

Trial Overview The trial tests daratumumab (anti-CD38 antibody) combined with a KRAS vaccine and nivolumab (anti-PD-1 antibody). It aims to see how well this mix controls cancer, its safety profile, and if it extends life expectancy. Patients will undergo regular monitoring through tests and procedures.

How Is the Trial Designed?

Group I: Refractory Non-Small Cell Lung Cancer Experimental Treatment 3 Interventions

Group II: Pancreatic Ductal Adenocarcinoma Experimental Treatment 3 Interventions

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Targovax ASA

Industry Sponsor

Trials

6

Recruited

200+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a study involving 93 patients with metastatic pancreatic cancer, combining GVAX vaccine and cyclophosphamide with nivolumab (Arm A) did not significantly improve overall survival compared to the same treatment without nivolumab (Arm B), with median survival times of 5.9 and 6.1 months, respectively.

Despite not meeting the primary endpoint, Arm A showed some objective tumor responses and beneficial immunologic changes in long-term survivors, such as increased CD8+ T cells, suggesting potential for immune modulation even if overall survival was similar to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer. Tsujikawa, T., Crocenzi, T., Durham, JN., et al.[2023]

Nivolumab, an anti-PD-1 immune checkpoint inhibitor used for cancer treatment, can induce severe immune-related adverse events, including a rare case of akathisia, which was not previously reported.

This case highlights the need for careful monitoring and documentation of all adverse events associated with nivolumab to improve management strategies for its diverse complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Induced Severe Akathisia in an Advanced Lung Cancer Patient. Abe, J., Sato, T., Tanaka, R., et al.[2019]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

The combination of GVAX vaccine with nivolumab and urelumab significantly increased the number of activated CD8+ CD137+ T cells in tumors, indicating a robust immune response, and was well-tolerated by patients.

While the median disease-free and overall survival rates were numerically improved with the combination therapy compared to other treatment arms, the results were not statistically significant, suggesting that further studies are needed to confirm these promising findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Heumann, T., Judkins, C., Li, K., et al.[2023]

Nivolumab, administered at 3 mg/kg with or without a peptide vaccine, was well tolerated and demonstrated a 25% response rate in patients with advanced melanoma, regardless of prior ipilimumab treatment.

The study suggests that nivolumab can induce long-lasting responses, with some patients responding for up to 140 weeks, and highlights the potential for combining or sequencing nivolumab with ipilimumab for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. Weber, JS., Kudchadkar, RR., Yu, B., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

In a study of 7 patients with advanced pancreatic ductal adenocarcinoma (PDA) receiving a WT1-targeting dendritic cell vaccine combined with chemotherapy, those who responded well (super-responders) had significantly lower levels of plasma matrix metalloproteinase-9 and systemic inflammatory markers compared to non-responders.

Lower cytoplasmic expression of WT1 in PDA cells was also associated with better overall survival, suggesting that both low inflammatory responses and low WT1 expression may serve as predictive markers for patient outcomes in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1. Ito, Z., Kan, S., Bito, T., et al.[2019]

The Phase I trial of the p53-targeting modified vaccinia Ankara (p53MVA) vaccine showed that it can enhance T-cell recognition of the p53 protein in patients with refractory gastrointestinal cancers.

However, the T-cell response was temporary, indicating that combining p53MVA with immunomodulatory agents may be necessary to achieve lasting clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming immunosuppression to enhance a p53MVA vaccine. Hardwick, N., Chung, V., Cristea, M., et al.[2021]

The Rotterdam PancrEAtic Cancer Vaccination-2 trial is investigating the safety and tolerability of a combination treatment using dendritic cell vaccines and an anti-CD40 agonistic antibody in patients with advanced pancreatic cancer, with a focus on those who have not responded to standard chemotherapy.

This phase I trial will include 12 to 18 patients and aims to assess treatment-induced immune responses and tumor-specific effects, potentially offering a new immunotherapy approach for a disease with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial). Lau, SP., van 't Land, FR., van der Burg, SH., et al.[2023]

Pancreatic cancer is highly lethal due to its immune privilege, characterized by an immunosuppressive environment and poor T cell infiltration, making traditional immunotherapies less effective.

Emerging evidence suggests that combining different immunotherapy strategies, such as checkpoint blockade and engineered T cells, may enhance treatment efficacy for pancreatic cancer, highlighting the need for innovative approaches in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and Prevention of Pancreatic Cancer. Morrison, AH., Byrne, KT., Vonderheide, RH.[2023]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

The combination of GVAX and 3.0 mg/kg ipilimumab is safe and tolerable for patients with metastatic castration-resistant prostate cancer (mCRPC), with manageable immune-related adverse events observed during the study.

Out of 28 patients, 25% experienced a significant decline in prostate-specific antigen levels, indicating potential efficacy of the treatment, particularly at the 3.0 mg/kg dose level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. van den Eertwegh, AJ., Versluis, J., van den Berg, HP., et al.[2021]

Citations

1. investor.jnj.com investor.jnj.com/investor-news/news-details/2025/U-S--FDA-Oncologic-Drugs-Advisory-Committee-votes-in-favor-of-the-benefit-risk-profile-of-DARZALEX-FASPRO-daratumumab-and-hyaluronidase-fihj-for-high-risk-smoldering-multiple-myeloma/default.aspx

U.S. FDA Oncologic Drugs Advisory Committee votes in favor ... The committee reviewed data from the AQUILA study, a Phase 3, randomized, open-label trial which evaluated the efficacy and safety of DARZALEX ...

2. jnj.com jnj.com/innovativemedicine/us/news-center/oncology/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than ...

3. cancerletter.com cancerletter.com/clinical-roundup/20241213_9i/

Darzalex Faspro-based regimens demonstrate improved ... Darzalex Faspro-based regimens demonstrate improved rates of MRD negativity and PFS. December 13, 2024 · Vol.50 No.46.

4. withpower.com withpower.com/trial/daratumumab-for-non-small-cell-lung-cancer-30e3b

Daratumumab for Non-Small Cell Lung Cancer Daratumumab has shown effectiveness in treating multiple myeloma, a type of blood cancer, by helping patients achieve a significant response to treatment. While ...

5. prnewswire.com prnewswire.com/news-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativ-302472089.html

DARZALEX FASPRO® (daratumumab and hyaluronidase ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

6. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... “The administration of daratumumab was associated with a good safety profile and non ... non-small cell lung cancer (NSCLC). Pre-clinical studies indicated that ...

7. darzalex.com darzalex.com/dvrd/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

8. onclive.com onclive.com/view/teclistamab-plus-daratumumab-boosts-survival-in-r-r-myeloma

Teclistamab Plus Daratumumab Boosts Survival in R ... Teclistamab plus daratumumab improved progression-free and overall survival in relapsed/refractory multiple myeloma after 1 to 3 lines of ...

9. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/fda-daratumumab-isatuximab-newly-diagnosed-myeloma

Darzalex Faspro, Sarclisa Approvals for Multiple Myeloma FDA recently approved Darzalex Faspro and Sarclisa combined with standard treatment regimens for people with newly diagnosed multiple ...