Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Exelixis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2024 → ongoing

Decision date (initial)

2024-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Exelixis, Inc.

External identifiers

EU CT number

2023-506308-24-00

ClinicalTrials.gov

NCT06082167

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy

To compare the efficacy of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with recurrent or metastatic head and neck squamous cell carcinoma

Secondary objectives 3

1. To compare OS, ORR and duration of response (DOR) by Investigator for zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with recurrent or metastatic head and neck squamous cell carcinoma
2. To assess safety and tolerability of zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in subjects with recurrent or metastatic head and neck squamous cell carcinoma
3. To evaluate the effect of zanzalintinib on specified biomarkers and pharmacokinetics when administered in combination with pembrolizumab in subjects with recurrent or metastatic head and neck squamous cell carcinoma

Conditions and MedDRA coding

Recurrent or metastatic head and neck squamous cell carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy Note: Subjects should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization if given as part of multimodal treatment for locally advanced disease is allowed. Note: The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
2. PD-L1 expression level Combined Positive Score (CPS) ≥ 1
3. Subjects with oropharynx cancer must have assessment of HPV status from tumor tissue, per p16 testing.
4. Measurable disease according to RECIST 1.1 determined by the Investigator.
5. Recovery to baseline or ≤ Grade 1 severity(CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) is clinically nonsignificant and/or stable on supportive therapy.
6. Age 18 years (or the legal age of consent in your country, if higher than 18) or older on the day of consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 ; with documented assessment of independent activities of daily living (ADLs) and physical activity, as appropriate and according to subject’s age.
8. Adequate organ and marrow function

Exclusion criteria 13

1. Nasopharynx, salivary gland or occult primary site (regardless of p16 status)
2. Has disease that is suitable for local therapy administered with curative intent
3. Has received prior systemic immunotherapy with zanzalintinib, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137), except for anti-PD-1 or anti-PD-L1 agents in the peri-operative setting if progression/recurrence occurred ≥12 months after its completion.
4. Life expectancy < 3 months and/or a rapidly progressing disease (eg, uncontrolled tumor pain), which should be reviewed in the context of prior systemic therapy in the curative setting and must be discussed with the Sponsor.
5. Had documented progressive disease within less than 6 months of completion of either curatively or palliatively intended systemic treatment (ie, chemotherapy) for HNSCC, in locally advanced HNSCC or peri-operative setting. Note: radiographic confirmation of progressive disease is required. If both histologic and radiographic confirmations are available, the earliest date should be considered for documentation purposes. Subjects who progressed within 6 months of systemic treatment in non-curative setting are also excluded.
6. Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy, such as radiation pneumonitis or fistulation, are not eligible
7. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to randomization
8. Positive hepatitis B surface antigen (HBsAg) test.
9. Positive hepatitis C virus (HCV) antibody test
10. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Complete wound healing from major or minor surgery must have occurred at least prior to randomization.
11. Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 28 days before randomization.
12. Pregnant or lactating females.
13. Administration of a live, attenuated vaccine within 30 days before randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Investigator

Secondary endpoints 6

1. Incidence and severity of AEs, SAEs, AECIs
2. Changes in laboratory parameters and vital signs
3. ORR and DOR per RECIST 1.1 by Investigator
4. Plasma concentration of zanzalintinib
5. Correlation measured between pharmacokinetics of zanzalintinib and selected biomarkers with respect to preliminary safety and efficacy outcomes
6. OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Exelixis Inc.

Sponsor organisation

Exelixis Inc.

Address

1851 Harbor Bay Parkway

City

Alameda

Postcode

94502-3010

Country

United States

Scientific contact point

Organisation

Exelixis Inc.

Contact name

Exelixis Clinical Trials

Public contact point

Organisation

Exelixis Inc.

Contact name

Exelixis Clinical Trials

Third parties 11

Locations

13 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 436 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications