Antibody-Drug Conjugate Therapy for Cancer

Recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, UGT1A1 inhibitors, CYP3A4 inducers, others

Disqualifiers: Brain metastases, Cardiovascular conditions, Corneal disorders, 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

Compensation: Varies

Number of Visits: 5

Duration: Up to 3 years

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of three specific treatments, known as antibody-drug conjugates (ADCs), against certain advanced or metastatic cancers. The treatments target specific proteins found in some tumors: Trop-2, nectin-4, and HER2, using drugs such as sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan. Each ADC delivers a potent drug directly to cancer cells, aiming to halt their growth. This approach suits patients whose solid tumors have high levels of Trop-2, nectin-4, or HER2 proteins and who have not responded to other treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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, there is a required 'washout period' (time without taking certain medications) from prior therapies before starting the study treatment. It's best to discuss your specific medications with the trial team to understand any necessary adjustments.

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

A previous study showed that enfortumab vedotin commonly causes side effects such as tiredness, nerve pain, and skin problems. About 33.5% of participants experienced nerve pain, and 24.5% had skin reactions. Most people handle these side effects well, but they can occur.

For sacituzumab govitecan, another study found that 70% of patients experienced a low white blood cell count. Nausea and diarrhea were also common, affecting 62% and 54% of participants, respectively. Serious side effects were less frequent and mainly involved low white blood cell counts.

Trastuzumab deruxtecan has also been studied. It often leads to a drop in white blood cells, with 65% of patients experiencing this. Serious side effects occurred in about 16.6% of participants. Common issues included nausea and lung problems, such as lung inflammation.

Each of these treatments has side effects, but they are generally manageable. Researchers continue to test these treatments, focusing on patient tolerance while seeking effective cancer therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to targeting cancer cells. Unlike traditional chemotherapy, which can harm both cancerous and healthy cells, these antibody-drug conjugates (ADCs) like enfortumab vedotin, sacituzumab govitecan, and trastuzumab deruxtecan, specifically target cancer cells, minimizing damage to normal cells. Each ADC works by attaching a potent anticancer drug to an antibody that binds to specific proteins on the surface of cancer cells—such as nectin-4, Trop-2, or HER2—delivering the drug directly to the cancer. This targeted delivery not only enhances effectiveness but also reduces side effects, offering a more precise way to treat certain cancers.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic solid tumors?

Research has shown that enfortumab vedotin, one of the treatments in this trial, holds promise for treating advanced cancers. One study reported that 65.9% of patients experienced significant tumor shrinkage. Sacituzumab govitecan, another treatment option in this trial, has also proven effective, with some studies indicating patients lived about 12 months on average. Trastuzumab deruxtecan, also tested in this trial, works well for HER2-positive cancers, significantly reducing tumors in patients who have already received other treatments. These treatments target specific proteins on cancer cells, delivering potent drugs directly to the tumors, which helps kill the cancer cells while sparing healthy cells. ^{6 7 8 9 10}

Who Is on the Research Team?

Funda Meric-Bernstam

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors that have high levels of Trop-2, nectin-4, or HER2 proteins. Candidates must have progressed beyond standard treatments or be intolerant to them. They should not be dependent on transfusions and must have a good performance status (able to carry out daily activities). Key organ functions need to meet specific criteria, and they must consent to tumor biopsies.

Inclusion Criteria

My bilirubin levels are within the normal range, or I have Gilbert syndrome with levels not exceeding three times the normal limit.

My cancer can be measured by tests or scans.

My liver enzymes are within the normal range, or slightly elevated if I have liver cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive antibody-drug conjugates (ADCs) based on their tumor's protein expression. Treatment cycles repeat every 21 or 28 days depending on the cohort.

Up to 3 years

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

Every 3 months in years 1-2, every 6 months in year 3

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Sacituzumab Govitecan
• Trastuzumab Deruxtecan

Trial Overview The study tests if personalized treatment with one of three antibody-drug conjugates (ADCs)—sacituzumab govitecan, enfortumab vedotin, trastuzumab deruxtecan—works against tumors expressing certain proteins. These ADCs are designed to deliver cancer-killing drugs directly to the tumor cells by attaching to specific proteins on their surface.

How Is the Trial Designed?

Group I: Screening (record review, IHC assay) Experimental Treatment 2 Interventions

SCREENING STEP 1: Patients who have previously undergone SOC RNA testing have the results of their SOC RNA testing reviewed. Patients whose tumor expresses an appropriate TOI by RNA testing proceed to screening step 2. SCREENING STEP 2: Patients have TOI expression testing at the protein level by IHC assay performed on previously collected tissue. Patients with high Trop-2 protein expression are assigned to Cohort A. Patients with high nectin-4 protein expression are assigned to Cohort B. Patients with high HER2 protein expression are assigned to cohort C.

Group II: Cohort C (trastuzumab deruxtecan) Experimental Treatment 7 Interventions

Patients receive trastuzumab deruxtecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients also undergo ECHO or MUGA at screening and on study. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.

Group III: Cohort B (enfortumab vedotin) Experimental Treatment 5 Interventions

Patients receive enfortumab vedotin IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.

Group IV: Cohort A (sacituzumab govitecan) Experimental Treatment 5 Interventions

Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Sacituzumab govitecan (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

In a phase I trial involving 23 patients with metastatic urothelial carcinoma, the combination of sacituzumab govitecan (SG) and enfortumab vedotin (EV) demonstrated a high objective response rate of 70%, with three patients achieving complete responses.

The study identified a safe dose for further testing, with 78% of patients experiencing grade ≥3 adverse events, indicating that while the treatment is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. McGregor, BA., Sonpavde, GP., Kwak, L., et al.[2023]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan is an FDA-approved antibody-drug conjugate that effectively targets Trop-2, which is overexpressed in various solid tumors, including metastatic triple-negative breast cancer and urothelial carcinoma.

This drug combines an anti-Trop-2 antibody with the SN-38 payload, an active metabolite of irinotecan, showcasing a novel mechanism of action that enhances the delivery of potent anticancer agents directly to tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. Vranic, S., Gatalica, Z.[2022]

Sacituzumab govitecan (SG) showed promising efficacy in treating advanced epithelial cancers, with partial response rates of 22.2% in endometrial cancer and 17.7% in small-cell lung cancer, indicating its potential as a treatment option.

The safety profile of SG was consistent with previous studies, with common treatment-related adverse events including neutropenia (57.8%) and nausea (62.6%), and a notable incidence of grade ≥3 neutropenia in patients with specific genetic variations (UGT1A1∗28 homozygotes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A., Messersmith, WA., Kio, EA., et al.[2021]

Sacituzumab govitecan (SG) is a promising treatment for HR+/HER2- metastatic breast cancer (MBC), particularly for patients whose cancer has progressed despite other therapies, as it targets the Trop-2 protein which is highly expressed in these tumors.

The ongoing Phase III TROPiCS-02 study is evaluating the efficacy of SG compared to standard treatment options, aiming to address the significant clinical need for effective therapies in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Rugo, HS., Bardia, A., Tolaney, SM., et al.[2021]

Sacituzumab govitecan, an antibody-drug conjugate that uses the active metabolite SN-38, shows promise in treating advanced cancers like triple-negative breast cancer, with a unique conjugation method that enhances drug delivery and minimizes side effects.

The drug has been granted Breakthrough Therapy status by the FDA and is currently under accelerated approval review, highlighting its potential efficacy and safety in patients with difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan. Goldenberg, DM., Sharkey, RM.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1558767324002489

Real-world Evidence for Enfortumab Vedotin in Patients ... Enfortumab vedotin demonstrated a 31% ORR in locally advanced/metastatic urothelial carcinoma patients with prior therapy lines. The median PFS and OS were 4.8 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37678672/

EV-301 long-term outcomes: 24-month findings from the ... Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively.

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01174-3/fulltext

Real-world clinical outcomes of sacituzumab govitecan ... In a large real-world cohort, SG after EV resulted in limited efficacy: ORR 11%, mPFS 2.1 months and mOS 6.0 months. Grade 3-4 neutropenia rates were 36%.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.736

Treatment, tolerability and outcomes of enfortumab vedotin ... First response evaluation was performed in 88 patients, of these the objective response rate (ORR) was 65.9% with 12.5% complete remissions.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831221

Enfortumab Vedotin With or Without Pembrolizumab in ... The findings suggest that enfortumab vedotin, especially combined with pembrolizumab, offers promising beneficial outcomes in metastatic urothelial carcinoma ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372787/

Post-marketing drug safety surveillance of enfortumab ... Clinical trials reported that the most common AEs for EV were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.553

Safety and efficacy of enfortumab vedotin in patients with ... Most common AEs were peripheral sensory neuropathy (33.5% any grade), skin toxicity (24.5%) and fatigue (22.9%). In pts >/= 75 yrs, females, and ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-bladder-cancer/149388-asco-gu-2024-safety-and-efficacy-of-enfortumab-vedotin-in-patients-with-metastatic-locally-advanced-urothelial-cancer-real-world-evidence-from-a-european-database.html

ASCO GU 2024: Safety and Efficacy of Enfortumab Vedotin ... The most common and relevant adverse events with EV are neurotoxicity, dermatologic toxicity/pruritis, and fatigue. Adverse events of special interest include ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S240584402413575X

Risk analysis of enfortumab vedotin: A real-world approach ... EV is generally considered a safe and well-tolerated drug; however, common adverse reactions still occur after its use. The most frequent (≥20 ...

10. ema.europa.eu ema.europa.eu/en/documents/product-information/padcev-epar-product-information_en.pdf

Padcev, INN-enfortumab vedotin - EMA At the recommended dose of 1.25 mg/kg, enfortumab vedotin did not prolong the mean QTc interval to any clinically relevant extent based on ECG data from a study ...