What side effects are associated with this type of intervention?

Common side effects of treatments targeting NK cells and T-cell activation signals, such as immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), include fatigue, rash, diarrhea, and pruritus. More severe adverse events can include pneumonitis, colitis, hepatitis, and endocrinopathies, which may require management with immunosuppressive agents like steroids. These side effects result from the immune system's heightened activity against both cancerous and normal tissues.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of solid tumors that enhance the immune response by targeting specific receptors on cancer cells. Notable examples include pembrolizumab and nivolumab, which are immune checkpoint inhibitors targeting PD-1, and ipilimumab, which targets CTLA-4. These drugs work by activating T-cells to attack cancer cells. Additionally, combination therapies such as nivolumab plus ipilimumab have been approved for various cancers, including melanoma and renal cell carcinoma. These treatments are similar to DF1001, which targets NK cells and T-cell activation signals to specific receptors on cancer cells.

What other types of research exist?

Promising alternatives to DF1001 for solid tumor patients include: 1) UniCAR T cells targeting EGFR-expressing cancer cells, which have shown efficient tumor cell lysis in vitro and in vivo; 2) Bicistronic CD19.22.BBζ CAR T cells, which have demonstrated enhanced cytokine production and efficacy in B-ALL, potentially adaptable for solid tumors; 3) Adjuvant therapies like nivolumab and pembrolizumab, which have shown improved recurrence-free survival in melanoma and could be considered for other solid tumors.

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DF1001 for Solid Cancers

Q: What is the mechanism of action of this treatment?

Immunotherapy treatments for solid tumors, such as those being studied in the DF1001 trial, work by harnessing the body's immune system to target and destroy cancer cells. These therapies often involve activating natural killer (NK) cells and T-cells, which are crucial components of the immune response. By directing these immune cells to specific receptors on cancer cells, such as HER2, these treatments can enhance the body's ability to recognize and attack tumors. This approach is significant for solid tumor patients because it offers a targeted method to combat cancer, potentially leading to more effective and less toxic treatments compared to traditional chemotherapy.

Phase 1 & 2

Recruiting

Research Sponsored by Dragonfly Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have at least 1+ expression of HER2 by IHC

Patient must have progressed after one line of systemic chemotherapy

Must not have

NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)

Angina pectoris requiring anti-anginal medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment called DF1001-001 that helps the immune system target and destroy cancer cells. It focuses on patients with certain types of cancers that have a protein called HER2. The treatment works by activating immune cells to recognize and attack these cancer cells.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune activation such as inflammation in different organs, infusion-related reactions which can occur during treatment administration, fatigue, possible blood disorders and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My cancer shows a low level of HER2 protein.

Select...

My cancer has worsened after one chemotherapy treatment.

Select...

My cancer has worsened despite treatment targeting PD-1/PD-L1.

Select...

I have hormone receptor-positive cancer and it worsened despite hormone therapy.

Select...

I am eligible for nivolumab treatment for my cancer.

Select...

I've had a first treatment with platinum, fluoropyridine, and an anti-PD-1.

Select...

My tumor is HER2 low based on specific tests.

Select...

I've had chemotherapy and PD-1/PD-L1 inhibitors for bladder cancer.

Select...

My cancer is advanced or has spread, and standard treatments have failed or don't exist.

Select...

My cancer shows HER2 presence through a special staining test.

Select...

I have received only one treatment for my cancer after it spread.

Select...

My cancer has been tested and shows HER2 activity.

Select...

My tumor is HER2 positive.

Select...

My cancer has a known increase in the ERBB2 gene.

Select...

My cancer tests show high levels of HER2.

Select...

My cancer is a type of bladder cancer that has spread.

Select...

My cancer has worsened after one chemotherapy treatment.

Select...

My lung cancer is at an advanced stage and tests show HER2 presence without erbb2 amplification.

Select...

My lung cancer is at an advanced stage and tests show an increase in the erbb2 gene.

Select...

I am mostly active and my doctor thinks I have at least 3 months to live.

Select...

I am eligible for nab-paclitaxel for my metastatic breast cancer and haven't had taxanes in the last 6 months.

Select...

My breast cancer is confirmed by lab tests and is advanced.

Select...

My condition worsened after my first treatment.

Select...

My cancer has worsened after my last treatment.

Select...

My cancer does not show high levels of HER2 protein.

Select...

I've had a first treatment with specific drugs and trastuzumab for my cancer.

Select...

I am 18 years old or older.

Select...

Standard treatments have failed me, and I haven't received nivolumab before.

Select...

My first treatment is for advanced triple-negative breast cancer.

Select...

My cancer has worsened after my last treatment.

Select...

My cancer came back or got worse after platinum chemotherapy.

Select...

My cancer is advanced and cannot be removed by surgery.

Select...

My esophageal cancer cannot be removed by surgery and may have spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My heart's pumping ability is significantly reduced.

Select...

I take medication for chest pain due to heart problems.

Select...

I have severe allergies to certain medications or uncontrolled asthma.

Select...

I have a serious heart valve problem.

Select...

I am legally unable to make my own medical decisions.

Select...

I have a serious heart condition.

Select...

I need extra oxygen or have severe shortness of breath at rest due to my advanced cancer.

Select...

I haven't needed strong immune system medications for a long condition, except for skin color loss, in the last 3 years.

Select...

I have a serious heart rhythm problem.

Select...

I have or had cancer spread to my brain or spinal cord.

Select...

I am unable to sign the consent form or follow the study's requirements.

Select...

I have a fast heartbeat (over 100 beats per minute) that is not under control.

Select...

I do not have significant infections like HIV or active hepatitis.

Select...

My cancer is growing quickly.

Select...

I have had an organ or stem cell transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assess Overall Response Rate

Assess number of adverse events observed during treatment with DF1001 in combination with Nab paclitaxel

Assess number of adverse events observed during treatment with DF1001 in combination with Nivolumab

+2 more

Secondary study objectives

Assess Best Overall Response by Investigator Assessment.

Assess Duration of Response by Investigator Assessment.

Assess Overall Response Rate by Investigator Assessment.

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

22Treatment groups

Experimental Treatment

Group I: Monotherapy DF1001 Safety/PK/PD ExpansionExperimental Treatment1 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 NSCLCExperimental Treatment1 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 Treatment1 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 CancerExperimental Treatment1 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 NSCLCExperimental Treatment1 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 Treatment1 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 Treatment1 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 CancerExperimental Treatment1 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 CancerExperimental Treatment1 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 AmplificationExperimental Treatment1 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 EscalationExperimental Treatment1 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 Treatment2 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 Treatment2 Interventions

Group XIV: Combo Therapy with DF1001 and Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in NSCLCExperimental Treatment2 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 ExpansionExperimental Treatment2 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 CancerExperimental Treatment2 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 NSCLCExperimental Treatment2 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 CancerExperimental Treatment2 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 CancerExperimental Treatment2 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 NivolumabExperimental Treatment2 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 ExpansionExperimental Treatment2 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-paclitaxelExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sacituzumab Govitecan-hziy

2021

Completed Phase 3

~580

Nab paclitaxel

2014

Completed Phase 2

~580

Nivolumab

2015

Completed Phase 3

~4010

0 / 48Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immunotherapy treatments for solid tumors, such as those being studied in the DF1001 trial, work by harnessing the body's immune system to target and destroy cancer cells. These therapies often involve activating natural killer (NK) cells and T-cells, which are crucial components of the immune response. By directing these immune cells to specific receptors on cancer cells, such as HER2, these treatments can enhance the body's ability to recognize and attack tumors. This approach is significant for solid tumor patients because it offers a targeted method to combat cancer, potentially leading to more effective and less toxic treatments compared to traditional chemotherapy.

Antibody-Drug Conjugates: Patient and Treatment Selection.