Ozuriftamab Vedotin for Head and Neck Cancer

Recruiting at 6 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

290 Participants Needed

Trial Summary

What is the purpose of this trial?

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 with recurrent or metastatic squamous cell carcinoma of the head and neck.

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.

What data supports the effectiveness of the drug Ozuriftamab Vedotin for head and neck cancer?

Research on similar treatments, like atezolizumab and nivolumab, which target the PD-1/PD-L1 pathway, shows promise in treating head and neck cancer by enhancing the immune system's ability to fight the cancer. These drugs have shown clinical activity and safety in trials, suggesting that Ozuriftamab Vedotin, which also involves PD-1 inhibitors, may be effective as well. ^{1 2 3 4 5}

What is known about the safety of PD-1 inhibitors for head and neck cancer?

PD-1 inhibitors, used in head and neck cancer treatment, generally have an acceptable safety profile. Common side effects include diarrhea, low thyroid function, and skin rash, with rare cases of serious lung inflammation. ^{4 6 7 8 9}

How is the drug Ozuriftamab Vedotin different from other treatments for head and neck cancer?

Ozuriftamab Vedotin is unique because it combines an antibody-drug conjugate (a targeted therapy that links an antibody to a drug) with a PD-1 inhibitor, which helps the immune system attack cancer cells. This dual approach may offer a novel way to treat head and neck cancer compared to existing treatments that typically use either PD-1 inhibitors or other forms of therapy separately. ^{1 3 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Inter-assay reliability of programmed cell death-ligand 1 in head and neck squamous cell carcinoma. [2022]

4. England 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. [2022]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]

8. England 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. [2019]

9. United States 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. [2021]

10. China pubmed.ncbi.nlm.nih.gov

[The research progress of PD-1/L1 inhibitors application in the treatment of head and neck squamous cell carcinoma]. [2023]

11. Greece pubmed.ncbi.nlm.nih.gov

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. [2021]