Ozuriftamab Vedotin for Head and Neck Cancer

No longer recruiting at 7 trial locations

Overseen By BioAtla Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BioAtla, Inc.

Must not be taking: PD-1/L1 inhibitors, Anti-CTLA-4

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, 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: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ozuriftamab Vedotin, an experimental drug, either alone or with other medications, for individuals with head and neck squamous cell carcinoma, a type of cancer. The researchers aim to determine the treatment's effectiveness and safety for those with cancer that has returned or spread. Participants might receive Ozuriftamab Vedotin alone or in combination with other drugs like pembrolizumab or cetuximab. Individuals with squamous cell carcinoma in areas such as the throat or mouth, who have not received previous treatments for their recurrent or metastatic cancer, might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ozuriftamab vedotin, used alone or with other treatments, is promising in terms of safety for people with head and neck cancer. One study found that patients tolerated the treatment well, even those who had tried several other treatments before. Reports indicated good disease control in patients who had previously used other therapies.

When combined with pembrolizumab, another cancer drug, studies showed ozuriftamab vedotin was generally well-tolerated. Patients did not experience severe side effects in early trials.

In another study, ozuriftamab vedotin was used with cetuximab, a treatment for head and neck cancer. This combination also appeared safe, with patients managing the treatment without major issues.

Overall, these findings suggest that ozuriftamab vedotin, whether used alone or in combination, is generally safe for people with head and neck cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ozuriftamab Vedotin for head and neck cancer because it targets specific proteins on cancer cells, potentially improving precision in treatment. Unlike standard treatments like chemotherapy and radiation, which affect both healthy and cancerous cells, Ozuriftamab Vedotin is an antibody-drug conjugate designed to deliver its toxic payload directly to cancer cells, minimizing damage to normal tissue. Additionally, the combination therapies being tested, including PD-1 inhibitors like pembrolizumab, aim to enhance the immune system's ability to fight cancer, offering a potentially more effective approach than existing options.

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

Research has shown that patients with head and neck cancer have experienced good disease control when treated with ozuriftamab vedotin, the drug under study in this trial. This drug targets a protein called ROR2, often found in large amounts in certain tumors. In this trial, some participants will receive ozuriftamab vedotin alone, while others will receive it with pembrolizumab, which boosts the immune system and may improve results. Another group will receive a combination with cetuximab, which has shown strong potential to fight tumors. Additionally, early results for adding BA3071, another immune therapy, are promising. Overall, these treatments, as part of different arms in this trial, show encouraging signs of effectiveness against this challenging cancer. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent or metastatic squamous cell carcinoma of the head and neck, who have failed one PD-1/L1 inhibitor treatment. They should not be candidates for curative surgery or radiation, must have measurable disease, good organ function, and an ECOG status of 0 or 1. Excluded are those with HIV, hepatitis B/C, pregnant/breastfeeding women, significant heart issues, or severe allergies to monoclonal antibodies.

Inclusion Criteria

I am fully active or can carry out light work.

My liver is working well.

My cancer is in the throat or mouth, can't be removed by surgery or cured with radiation, and has spread.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have HIV, active hepatitis B, or hepatitis C.

I have never had a severe allergic reaction to antibody treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BA3021 as monotherapy or in combination therapy with pembrolizumab, cetuximab, or BA3071

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ozuriftamab Vedotin
• PD-1 inhibitor

Trial Overview The study tests BA3021 in patients whose cancer has returned or spread and expresses ROR-2 after failing treatments that block PD-1/L1 proteins. It's a Phase 2 trial where all participants receive the same experimental therapy without being compared to another group.

How Is the Trial Designed?

Group I: Cohort N1 Experimental Treatment 3 Interventions

Neoadjuvant/induction setting combination therapy of BA3021 2Q3W dosing regimen, pembrolizumab Q3W dosing regimen, and BA3071 Q3W dosing regimen prior to surgery.

Group II: Cohort M2 Experimental Treatment 1 Intervention

Monotherapy BA3021 2Q3W dosing regimen

Group III: Cohort M1 Experimental Treatment 1 Intervention

Monotherapy BA3021 Q2W dosing regimen

Group IV: Cohort C3 Experimental Treatment 2 Interventions

Combination therapy of BA3021 2Q3W dosing regimen and cetuximab QW dosing regimen

Group V: Cohort C2 Experimental Treatment 2 Interventions

Combination therapy of BA3021 2Q3W dosing regimen, and pembrolizumab Q3W dosing regimen

Group VI: Cohort C1 Experimental Treatment 3 Interventions

Combination therapy of BA3021 2Q3W dosing regimen, pembrolizumab Q3W dosing regimen, and BA3071 Q3W dosing regimen

Ozuriftamab Vedotin is already approved in United States for the following indications:

Approved in United States as Ozuriftamab vedotin for:

• Recurrent or metastatic squamous cell carcinoma of the head and neck (Fast Track designation)

Who Is Running the Clinical Trial?

BioAtla, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Published Research Related to This Trial

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

The FDA has approved various PD-1/L1 inhibitors for treating advanced head and neck squamous cell carcinoma, including options for monotherapy and combinations with chemoradiotherapy and targeted therapies.

Recent research highlights the efficacy of these immunotherapies, suggesting they can lead to more precise and individualized treatment plans for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The research progress of PD-1/L1 inhibitors application in the treatment of head and neck squamous cell carcinoma]. Song, P., Yan, X., Jiang, Y., et al.[2023]

The 22C3 laboratory developed test (LDT) for PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) shows almost perfect concordance with the standardized 22C3 pharmDx assay, indicating it can reliably identify patients who may benefit from pembrolizumab treatment.

Both assays demonstrated substantial interobserver agreement and similar levels of intratumor heterogeneity, confirming that the LDT is a safe and effective alternative to the pharmDx assay for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inter-assay reliability of programmed cell death-ligand 1 in head and neck squamous cell carcinoma. Hempenius, MA., Bisheshar, SK., Slagter-Menkema, L., et al.[2022]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

In a phase 3 trial involving 286 patients with recurrent squamous-cell carcinoma of the head and neck, zalutumumab did not significantly increase overall survival compared to best supportive care, but it did extend progression-free survival, indicating some efficacy in delaying disease progression.

Zalutumumab was generally safe, with dose adjustments based on skin rash, though it was associated with higher rates of grade 3-4 adverse events like rash and infections compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Machiels, JP., Subramanian, S., Ruzsa, A., et al.[2022]

In a phase 3 trial involving 361 patients with recurrent squamous-cell carcinoma of the head and neck, nivolumab significantly improved overall survival compared to standard therapy, with a median survival of 7.5 months versus 5.1 months.

Nivolumab also had a better safety profile, with fewer severe treatment-related adverse events (13.1% vs. 35.1% in standard therapy), and patients reported stable quality of life compared to those receiving standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. Ferris, RL., Blumenschein, G., Fayette, J., et al.[2022]

In a study of 221 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, cetuximab combined with platinum-based therapy showed a median progression-free survival of 6.5 months and overall survival of 10.8 months, indicating its efficacy in a real-world setting.

The treatment was generally well-tolerated, with 39.8% of patients experiencing grade ≥3 adverse events, and only 5.4% of serious adverse events were related to cetuximab, suggesting a manageable safety profile similar to that observed in the pivotal phase III EXTREME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line cetuximab + platinum-based therapy for recurrent/metastatic head and neck squamous cell carcinoma: A real-world observational study-ENCORE. Le Tourneau, C., Ghiani, M., Cau, MC., et al.[2023]

In a study of 12 patients with recurrent and metastatic nasopharyngeal carcinoma (R/M-NPC) treated with nivolumab, the 1-year survival rate was 75.8%, indicating that this treatment can provide significant survival benefits.

Nivolumab demonstrated a modest overall response rate of 16.7% and a disease control rate of 41.7%, suggesting it is a relatively safe second-line therapy for R/M-NPC, even for patients who do not show a strong response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. Sato, H., Fushimi, C., Okada, T., et al.[2021]

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05271604

NCT05271604 | A Phase 2 Open Label Study of BA3021 in ... This is a multi-center, open-label Phase 2 study designed to evaluate the efficacy and safety of BA3021 as monotherapy and combination therapy in patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12460141/

Head and neck cancer – emerging targeted therapies - PMC Collectively, this data suggests its potential to provide significant antitumor activity in both treatment-naïve and heavily pretreated HNSCC ...

3. ir.bioatla.com ir.bioatla.com/news-releases/news-release-details/bioatla-presents-phase-2-ozuriftamab-vedotin-oz-v-clinical-trial

BioAtla Presents Phase 2 Ozuriftamab Vedotin (Oz-V) ... Other studies using standard of care agents (methotrexate, docetaxel, or cetuximab) have reported ORR of 3.4% and OS of 4.4 months among HPV+ ...

4. onclive.com onclive.com/view/fda-provides-guidance-on-registrational-path-for-ozuriftamab-vedotin-in-oropharyngeal-squamous-cell-carcinoma

FDA Provides Guidance on Registrational Path for ... BioAtla presents phase 2 ozuriftamab vedotin (oz-v) clinical trial data demonstrating compelling antitumor activity in HPV-associated ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S030573722500060X

Management approaches for recurrent or metastatic head ... Immunotherapy resistance is an emerging problem in HNSCC. Underlying mechanisms and optimal treatment for resistant patients are unclear.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02448-7/fulltext

868P Phase II trial of ozuriftamab vedotin (BA3021), a ... BA3021, a CAB-ROR2-ADC, conditionally and reversibly binds to ROR2 and internalizes under low pH conditions in tumors.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988251/

Preclinical development of ozuriftamab vedotin (BA3021) ... Early clinical results with BA3021 (ozuriftamab vedotin) have shown promising outcomes in patients with advanced malignancies, including ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6048

Phase 2 trial of ozuriftamab vedotin (BA3021), a ... Head and Neck Cancer May 2023. A phase 2 open-label study of conditionally active biologic ozuriftamab vedotin (BA3021) in failed PD-1/L1 ...