DF1001 for Solid Cancers

Recruiting at 63 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dragonfly Therapeutics

Must not be taking: Steroids, Immunosuppressants, Investigational drugs

Disqualifiers: CNS metastases, Autoimmune disease, Serious cardiac illness, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

378 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called DF1001, designed to boost the body's immune response against cancer by targeting specific proteins on cancer cells. It focuses on solid tumors linked to a protein called HER2, found in several cancers such as non-small cell lung cancer, breast cancer, and gastric cancer. The trial tests DF1001 alone and in combination with other treatments to determine the best and safest dose. Patients who may be suitable have cancers with HER2 involvement and have experienced disease progression despite previous treatments. As a Phase 1 trial, this research aims to understand how DF1001 works in people, offering patients the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any concurrent anticancer treatments or certain other therapies, so it's best to discuss your specific medications with the trial team.

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

Research has shown that DF1001 is generally safe when used alone. In one study, 106 patients took DF1001 by itself, and it was well-tolerated, with no severe side effects reported.

Researchers also assessed the safety of DF1001 when combined with other drugs like nab-paclitaxel or nivolumab. These combinations aim to enhance the immune system's ability to fight cancer. Previous studies on similar drug combinations have shown they are usually safe, though they might cause mild to moderate side effects like tiredness or nausea, which are common in cancer treatments.

The current DF1001 study focuses on determining the right dose and ensuring safety. Although the research remains in its early stages, the treatment's performance so far provides some confidence in its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DF1001 because it targets HER2, a protein that can contribute to cancer growth, in a novel way. Unlike traditional therapies that might focus broadly on killing cancer cells, DF1001 is designed to activate the body's immune system specifically against tumors with HER2 activation. This targeted approach could potentially lead to more effective treatments with fewer side effects. Additionally, when combined with other drugs like nivolumab or nab-paclitaxel, DF1001 could enhance the immune response and improve outcomes for patients with various types of solid tumors. This unique mechanism and potential for combination therapy make DF1001 a promising candidate in cancer treatment.

What evidence suggests that this trial's treatments could be effective?

Research has shown that DF1001 has promising effects against tumors in patients with certain types of cancer that exhibit varying levels of the protein HER2. Earlier studies found DF1001 to be generally safe, with patients experiencing encouraging reductions in tumor size. In this trial, some participants will receive DF1001 combined with Nab-paclitaxel, a cancer drug with fewer side effects, which has demonstrated positive results in reducing tumors. Others will receive DF1001 with Nivolumab, a drug that aids the immune system in fighting cancer, which was also well-tolerated and is under study for its potential benefits. These findings suggest that DF1001, either alone or in combination with other treatments, could be an effective option for some HER2-positive cancers. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults with various advanced solid tumors, especially those expressing HER2. Participants must have measurable disease and adequate organ function, and women of childbearing age must use effective contraception. Excluded are individuals with recent other cancers, CNS metastases, severe heart conditions, uncontrolled infections or allergies to monoclonal antibodies.

Inclusion Criteria

I have been treated with trastuzumab, pertuzumab, and a HER2-targeting ADC.

My liver is working well.

My cancer shows a low level of HER2 protein.

Exclusion Criteria

My heart's pumping ability is significantly reduced.

I have mild side effects from previous treatments, but hair loss and mild nerve issues are okay.

I have not taken any drugs recently that are not allowed in the trial, but I have previously taken HER2-targeting treatments with the required break period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive increasing doses of DF1001 to determine the maximum tolerated dose

Varies per cohort

Dose Expansion

Participants receive the recommended phase 2 dose (RP2D) of DF1001, either as monotherapy or in combination with other drugs

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last treatment

What Are the Treatments Tested in This Trial?

Interventions

• DF1001
• Nab paclitaxel
• Nivolumab

Trial Overview The trial is testing DF1001's ability to activate immune cells against cancer in two phases: dose escalation (finding the right amount) and expansion (testing that amount more broadly). It will be combined with nivolumab or Nab paclitaxel in patients whose tumors express HER2.

How Is the Trial Designed?

Group I: Monotherapy DF1001 Safety/PK/PD Expansion Experimental Treatment 1 Intervention

Expansion cohorts of monotherapy DF1001 in multiple dose levels after evaluation for safety in Monotherapy Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.

Group II: Monotherapy DF1001 Exploratory Efficacy Expansion in NSCLC Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documentation of HER2 activation.

Group III: Monotherapy DF1001 Exploratory Efficacy Expansion in Metastatic Breast Cancer (HR+/HER2-) Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documentation of HR positive and HER2 negative expression.

Group IV: Monotherapy DF1001 Expansion in Urothelial Bladder Cancer Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with urothelial bladder cancer using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group V: Monotherapy DF1001 Expansion in NSCLC Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documented erbb2 amplification using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group VI: Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 Low) Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group VII: Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 High) Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group VIII: Monotherapy DF1001 Expansion in Gastric Cancer Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with gastric cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group IX: Monotherapy DF1001 Expansion in Esophageal Cancer Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20 patients with esophageal cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group X: Monotherapy DF1001 Expansion in Cancers with Erbb2 Amplification Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 40 patients with solid tumors showing documented erbb2 amplification using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Group XI: Monotherapy DF1001 Dose Escalation Experimental Treatment 1 Intervention

Dose escalation cohorts of DF1001 in sequential ascending order.

Group XII: DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HR+/HER2-) Experimental Treatment 2 Interventions

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 40 patients, including safety lead-in, with metastatic breast cancer with documentation of HR positive and HER2 negative expression.

Group XIII: DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HER2+) Experimental Treatment 2 Interventions

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 40 patients, including safety lead-in, with metastatic breast cancer with documentation of HER2 positive expression.

Group XIV: Combo Therapy with DF1001 and Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in NSCLC Experimental Treatment 2 Interventions

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 20 patients, including safety lead-in, with non-small cell lung cancer with documentation of HER2 activation.

Group XV: Combination Therapy with DF1001 and Nivolumab Safety/PK/PD Expansion Experimental Treatment 2 Interventions

Expansion cohort of DF1001 in combination with nivolumab after evaluation for safety in the Combination Therapy with DF1001 and nivolumab Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.

Group XVI: Combination Therapy with DF1001 and Nivolumab Expansion in Urothelial Bladder Cancer Experimental Treatment 2 Interventions

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with urothelial bladder cancer using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Group XVII: Combination Therapy with DF1001 and Nivolumab Expansion in NSCLC Experimental Treatment 2 Interventions

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Group XVIII: Combination Therapy with DF1001 and Nivolumab Expansion in Gastric Cancer Experimental Treatment 2 Interventions

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with gastric cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Group XIX: Combination Therapy with DF1001 and Nivolumab Expansion in Esophageal Cancer Experimental Treatment 2 Interventions

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with esophageal cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Group XX: Combination Therapy with DF1001 and Nivolumab Experimental Treatment 2 Interventions

Combination dose escalation of DF1001 in combination with nivolumab in patients with select solid tumors.

Group XXI: Combination Therapy with DF1001 and Nab-paclitaxel Safety/PK/PD Expansion Experimental Treatment 2 Interventions

Expansion cohort of DF1001 in combination with nab-paclitaxel after evaluation for safety in the Combination Therapy with DF1001 and nab-paclitaxel Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.

Group XXII: Combination Therapy with DF1001 and Nab-paclitaxel Experimental Treatment 2 Interventions

Combination dose escalation of DF1001 in combination with nab-paclitaxel in patients with select solid tumors.

DF1001 is already approved in United States for the following indications:

Approved in United States as DF1001 for:

• Esophageal cancer (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Dragonfly Therapeutics

Lead Sponsor

Trials

4

Recruited

1,300+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2508

Phase 1/2 Study of DF1001, a novel tri-specific, NK cell ... DF1001 monotherapy demonstrates promising anti-tumor activity in treatment refractory patients with a spectrum of HER2 expression as well as MOA ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04143711

Study of DF1001 in Patients with Advanced Solid Tumors DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells.

3. dragonflytx.com dragonflytx.com/post/dragonfly-therapeutics-announces-the-presentation-of-phase-1-df1001-trinket-dose-escalation-results

Dragonfly Therapeutics Announces the Presentation of Phase ... DF1001 was safe and well tolerated as monotherapy at biweekly doses up to 15 mg/kg and has successfully progressed through Phase 1 combinations ...

4. meetings.asco.org meetings.asco.org/abstracts-presentations/218294

Phase 1 DF1001 monotherapy dose-escalation results. DF1001 monotherapy demonstrates promising anti-tumor activity in treatment refractory patients with a spectrum of HER2 expression as well as MOA consistent ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04143711

Study of DF1001 in Patients with Advanced Solid Tumors DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells.

6. mountsinai.org mountsinai.org/clinical-trials/study-of-df1001-in-patients-with-advanced-solid-tumors

Study of DF1001 in Patients with Advanced Solid Tumors Summary: DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells.