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AzTrials

Head and Neck Squamous Cell CarcinomaPhase 2/3STELLAR-305NCT06082167

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

A Phase 2/3 study testing Zanzalintinib and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Exelixis at 168 sites in 26 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a multicenter, randomized, double-blind, controlled Phase 2/3 trial of zanzalintinib in combination with pembrolizumab versus zanzalintinib-matched placebo in combination with pembrolizumab in subjects with programmed death-ligand 1 (PD-L1) positive recurrent or metastatic head and neck squamous cell carcinoma… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Zanzalintinib and Pembrolizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
600 participants
Where
168 sitesin 26 countries
Study dates
7 Jun 2024to Mar 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapy.
  • 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.
  • The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, and larynx.
  • PD-L1 expression level Combined Positive Score (CPS) ≥ 1.
  • Participants with oropharyngeal cancer must have human papillomavirus (HPV) status from tumor tissue.
  • Measurable disease according to RECIST 1.1 as determined by the Investigator.
Show all 11Show fewer
  • Tumor samples (archival or fresh tumor biopsy) are required. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.
  • Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Age 18 years (or the legal age of consent in your country, if higher than 18) or older on the day of consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Adequate organ and marrow function.

Who cannot join

  • Nasopharynx, salivary gland or occult primary site (regardless of p16 status).
  • Has disease that is suitable for local therapy administered with curative intent.
  • Has received prior therapy 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 (for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
  • Life expectancy < 3 months.
  • Had progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
  • Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
Show all 13Show fewer
  • 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.
  • Positive hepatitis B surface antigen (HBsAg) test.
  • Positive hepatitis C virus (HCV) antibody test.
  • 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.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 28 days before randomization.
  • Pregnant or lactating females.
  • Administration of a live, attenuated vaccine within 30 days before randomization.

Trial locations and contacts

168 sites in 26 countries.

168 sites in 26 countries

Brazil16 sites

  • Exelixis Clinical Site #116

    Barretos, 14784 400

  • Exelixis Clinical Site #75

    Curitiba, 80810 050

  • Exelixis Clinical Site #101

    Curitiba, 81520 060

  • Exelixis Clinical Site #110

    Jaú, São Paulo, 17210 190

  • Exelixis Clinical Site #68

    Passo Fundo, Rio Grande do Sul, 99010-260

  • Exelixis Clinical Site #90

    Porto Alegre, Rio Grande do Sul, 91350 200

  • Exelixis Clinical Site #97

    Porto Alegre, 90110 270

  • Exelixis Clinical Site #102

    Recife, 50070 225

  • Exelixis Clinical Site #87

    Rio de Janeiro, 20230 130

  • Exelixis Clinical Site #65

    Santo André, São Paulo, 09060-650

  • Exelixis Clinical Site #83

    São José do Rio Preto, São Paulo, 15090 000

  • Exelixis Clinical Site #76

    São Paulo, 01323 030

  • Exelixis Clinical Site #77

    São Paulo, 01525 001

  • Exelixis Clinical Site #67

    São Paulo, 04014-002

  • Exelixis Clinical Site #98

    São Paulo, 05403 900

  • Exelixis Clinical Site #88

    São Paulo, 1221020

Other trials in Brazil

United States15 sites

  • Exelixis Clinical Site #123

    Athens, Georgia, 30607

  • Exelixis Clinical Site #82

    Atlanta, Georgia, 30322

  • Exelixis Clinical Site #158

    Camden, New Jersey, 08103

  • Exelixis Clinical Site #19

    Chicago, Illinois, 60611

  • Exelixis Clinical Site #62

    Des Moines, Iowa, 50309

  • Exelixis Clinical Site #95

    Durham, North Carolina, 27710

  • Exelixis Clinical Site #2

    Fullerton, California, 92835

  • Exelixis Clinical Site #100

    Iowa City, Iowa, 52242

  • Exelixis Clinical Site #148

    Lebanon, New Hampshire, 03756

  • Exelixis Clinical Site #1

    Orange City, Florida, 32763

  • Exelixis Clinical Site #43

    Roanoke, Virginia, 24014

  • Exelixis Clinical Site #3

    Shirley, New York, 11967

  • Exelixis Clinical Site #4

    St Louis, Missouri, 63110

  • Exelixis Clinical Site #163

    Tampa, Florida, 33612-9497

  • Exelixis Clinical Site #117

    Wilson, North Carolina, 27893

Other trials in United States

France13 sites

  • Exelixis Clinical Site #16

    Bordeaux, Gironde, 33075

  • Exelixis Clinical Site #144

    Dijon, 21000

  • Exelixis Clinical Site #141

    Grenoble, 09 38043

  • Exelixis Clinical Site #107

    Le Mans, Sarthe, 72000

  • Exelixis Clinical Site #140

    Lille, 59000

  • Exelixis Clinical Site #70

    Lyon, Rhone, 69008

  • Exelixis Clinical Site #28

    Marseille, Bouches-du-Rhône, 13005

  • Exelixis Clinical Site #26

    Paris, 75013

  • Exelixis Clinical Site #112

    Pierre-Bénite, 69004

  • Exelixis Clinical Site #105

    Poitiers, 86021

  • Exelixis Clinical Site #44

    Rennes, Ille Et Vilaine, 35042

  • Exelixis Clinical Site #108

    Saint Priest En Jarez, Pays de la Loire Region, 42270

  • Exelixis Clinical Site #66

    Villejuif, Val De Marne, 94805

Other trials in France

South Korea12 sites

  • Exelixis Clinical Site #7

    Busan, Gangwon-do, 49267

  • Exelixis Clinical Site #13

    Busan, 49201

  • Exelixis Clinical Site #69

    Jeonju, Jeollabuk-do, 54907

  • Exelixis Clinical Site #8

    Jeonju, Jeollabuk-do, 54907

  • Exelixis Clinical Site #5

    Seoul, 3722

  • Exelixis Clinical Site #63

    Seoul, 5505

  • Exelixis Clinical Site #12

    Seoul, 6273

  • Exelixis Clinical Site #6

    Seoul, 6591

  • Exelixis Clinical Site #29

    Seoul, 8308

  • Exelixis Clinical Site #30

    Suwon, Gyeonggi-do, 16247

  • Exelixis Clinical Site #17

    Suwon, Gyeonggi-do, 16499

  • Exelixis Clinical Site #9

    Yangsan, Gyeongsangnam-do, 50612

Other trials in South Korea

Spain12 sites

  • Exelixis Clinical Site #130

    A Coruña, 15009

  • Exelixis Clinical Site #115

    Barcelona, 08025

  • Exelixis Clinical Site #113

    Girona, 17007

  • Exelixis Clinical Site #134

    Madrid, 28027

  • Exelixis Clinical Site #111

    Madrid, 28033

  • Exelixis Clinical Site #32

    Madrid, 28034

  • Exelixis Clinical Site #59

    Madrid, 28040

  • Exelixis Clinical Site #31

    Madrid, 28046

  • Exelixis Clinical Site #136

    Pamplona, 31008

  • Exelixis Clinical Site #126

    Seville, 41009

  • Exelixis Clinical Site #153

    Valencia, 46009

  • Exelixis Clinical Site #41

    Zaragoza, 50009

Other trials in Spain

Italy9 sites

  • Exelixis Clinical Site #35

    Brescia, 25124

  • Exelixis Clinical Site #21

    Candiolo, Torino, 10060

  • Exelixis Clinical Site #45

    Catania, 95123

  • Exelixis Clinical Site #81

    Milan, 20133

  • Exelixis Clinical Site #55

    Milan, 20141

  • Exelixis Clinical Site #18

    Naples, 80131

  • Exelixis Clinical Site #78

    Rome, 0168

  • Exelixis Clinical Site #124

    Rozzano, 20089

  • Exelixis Clinical Site #10

    Verona, 37134

Other trials in Italy

Argentina8 sites

  • Exelixis Clinical Site #91

    Buenos Aires, C1428AQK

  • Exelixis Clinical Site # 47

    Ciudad Autonoma de Buenos Aire, C1015ABO

  • Exelixis Clinical Site #53

    Ciudad Autonoma de Buenos Aire, C1056ABJ

  • Exelixis Clinical Site #93

    Córdoba, X5000JHQ

  • Exelixis Clinical Site #64

    Córdoba, X5008HHW

  • Exelixis Clinical Site #157

    Pergamino, B2700CPM

  • Exelixis Clinical Site #73

    Rosario, Santa Fe Province, S2000KZE

  • Exelixis Clinical Site #92

    Santa Fe, S3000FFU

Other trials in Argentina

Chile7 sites

  • Exelixis Clinical Site #33

    Santiago, 13127

  • Exelixis Clinical Site #52

    Santiago, 7500859

  • Exelixis Clinical Site #38

    Santiago, 8331143

  • Exelixis Clinical Site #109

    Santiago, 8940577

  • Exelixis Clinical Site #50

    Talca, 3465586

  • Exelixis Clinical Site #51

    Valdivia, 5090000

  • Exelixis Clinical Site #40

    Viña del Mar, 2540364

Other trials in Chile

Czechia6 sites

  • Exelixis Clinical Site #49

    Nový Jičín, 74101

  • Exelixis Clinical Site #58

    Olomouc, 77900

  • Exelixis Clinical Site #151

    Prague, 10 10034

  • Exelixis Clinical Site #34

    Prague, 14059

  • Exelixis Clinical Site #48

    Prague, 15006

  • Exelixis Clinical Site #36

    Prague, 18081

Other trials in Czechia

Greece6 sites

  • Exelixis Clinical Site #155

    Athens, 11527

  • Exelixis Clinical Site #129

    Athens, 12462

  • Exelixis Clinical Site #159

    Larissa, 41500

  • Exelixis Clinical Site #120

    Thessaloniki, 54622

  • Exelixis Clinical Site #150

    Thessaloniki, 56403

  • Exelixis Clinical Site #128

    Thessaloniki, 57001

Other trials in Greece

Romania6 sites

  • Exelixis Clinical Site #160

    Bucharest, 030463

  • Exelixis Clinical Site #24

    Cluj-Napoca, 400641

  • Exelixis Clinical Site #20

    Craiova, 200542

  • Exelixis Clinical Site #104

    Floreşti, 407280

  • Exelixis Clinical Site #127

    Ploieşti, 100337

  • Exelixis Clinical Site #143

    Timișoara, 300239

Other trials in Romania

Australia5 sites

  • Exelixis Clinical Site # 46

    Adelaide, 5000

  • Exelixis Clinical Site #154

    Bedford Park, 5042

  • Exelixis Clinical Site #137

    Camperdown, NSW 2050

  • Exelixis Clinical Site #39

    Murdoch, 6150

  • Exelixis Clinical Site #57

    Port Macquarie, New South Wales, 2444

Other trials in Australia

Bulgaria5 sites

  • Exelixis Clinical Site #25

    Plovdiv, 4004

  • Exelixis Clinical Site #94

    Rousse, 7002

  • Exelixis Clinical Site #15

    Sofia, 1330

  • Exelixis Clinical Site #11

    Sofia, 1527

  • Exelixis Clinical Site #54

    Sofia, 1797

Other trials in Bulgaria

Colombia5 sites

  • Exelixis Clinical Site #96

    Barranquilla, 80020

  • Exelixis Clinical Site #152

    Bogotá, 129

  • Exelixis Clinical Site #103

    Floridablanca, 6810002

  • Exelixis Clinical Site #146

    Pasto, 520001

  • Exelixis Clinical Site #149

    Pereira, 660001

Other trials in Colombia

Israel5 sites

  • Exelixis Clinical Site #132

    Haifa, 3109601

  • Exelixis Clinical Site #85

    Haifa, 3436212

  • Exelixis Clinical Site #74

    Jerusalem, 911201

  • Exelixis Clinical Site #122

    Ramat Gan, 5265601

  • Exelixis Clinical Site #86

    Tel Aviv, 6423906

Other trials in Israel

Taiwan5 sites

  • Exelixis Clinical Site #145

    Kaohsiung City, 807

  • Exelixis Clinical Site #164

    Taichung, 40447

  • Exelixis Clinical Site #118

    Taipei, 100229

  • Exelixis Clinical Site #142

    Taipei, 11217

  • Exelixis Clinical Site #165

    Taoyuan, 33305

Other trials in Taiwan

United Kingdom5 sites

  • Exelixis Clinical Site #135

    London, England, SW36JJ

  • Exelixis Clinical Site #138

    Manchester, M20 4BX

  • Exelixis Clinical Site #84

    Romford, Essex, RM7 0AG

  • Exelixis Clinical Site #133

    Sutton, SM2 5PT

  • Exelixis Clinical Site #161

    Torquay, TQ2 7AA

Other trials in United Kingdom

Belgium4 sites

  • Exelixis Clinical Site #22

    Brussels, 1200

  • Exelixis Clinical Site #106

    Charleroi, 6000

  • Exelixis Clinical Site #14

    Libramont, 6800

  • Exelixis Clinical Site #37

    Sint-Niklaas, 9100

Other trials in Belgium

Hungary4 sites

  • Exelixis Clinical Site #125

    Budapest, 1083

  • Exelixis Clinical Site #99

    Kecskemét, 6000

  • Exelixis Clinical Site #131

    Salgótarján, 3100

  • Exelixis Clinical Site #147

    Szekszárd, 7100

Other trials in Hungary

Thailand4 sites

  • Exelixis Clinical Site #80

    Bangkok, 10330

  • Exelixis Clinical Site #71

    Bangkoknoi, Bangkok, 10700

  • Exelixis Clinical Site #56

    Chiang Mai, Chiang Mai, 50200

  • Exelixis Clinical Site #79

    Hat Yai, Changwat Songkhla, 90110

Other trials in Thailand

Austria3 sites

  • Exelixis Clinical Site #156

    Linz, 4010

  • Exelixis Clinical Site #42

    Salzburg, 5020

  • Exelixis Clinical Site #166

    Vienna, 1090

Other trials in Austria

Malaysia3 sites

  • Exelixis Clinical Site #60

    Kuala Lumpur, 50586

  • Exelixis Clinical Site #72

    Kuala Lumpur, 59100

  • Exelixis Clinical Site #61

    Putrajaya, Kuala Lumpur, 62250

Other trials in Malaysia

Mexico3 sites

  • Exelixis Clinical Site #114

    Guadalajara, Jalisco, 44160

  • Exelixis Clinical Site #168

    Guadalajara, 44280

  • Exelixis Clinical Site #119

    San Juan del Río, Querétaro, 76800

Other trials in Mexico

Poland3 sites

  • Exelixis Clinical Site #139

    Gliwice, 44 102

  • Exelixis Clinical Site #89

    Piotrków, Trybunalski, 97 300

  • Exelixis Clinical Site #162

    Torun, 87 100

Other trials in Poland

Slovakia3 sites

  • Exelixis Clinical Site #23

    Košice, 04191

  • Exelixis Clinical Site #27

    Trnava, 91775

  • Exelixis Clinical Site #121

    Žilina, 01207

Other trials in Slovakia

Germany1 site

  • Exelixis Clinical Site #167

    Giessen, 35392

Other trials in Germany

About this study

Official title: A Phase 2/3, Randomized, Double-Blind, Controlled Study of Zanzalintinib (XL092) in Combination With Pembrolizumab vs Pembrolizumab in First-Line Treatment of Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

This is a multicenter, randomized, double-blind, controlled Phase 2/3 trial of zanzalintinib in combination with pembrolizumab versus zanzalintinib-matched placebo in combination with pembrolizumab in subjects with programmed death-ligand 1 (PD-L1) positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) incurable by local therapies who have not received prior systemic therapy for recurrent or metastatic disease.

Being tested
Zanzalintinib, Zanzalintinib-matched Placebo, Pembrolizumab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanzalintinibDrug

    Also called XL092

    Specified doses on specified days

  • Zanzalintinib-matched PlaceboDrug

    Also called XL092-matched Placebo

    Specified doses on specified days

  • PembrolizumabBiological

    Also called KEYTRUDA®

    Specified doses on specified days

Study groups in NCT06082167
Study groupRoleWhat they receive
Zanzalintinib + PembrolizumabExperimentalSubjects with R/M HNSCC will receive zanzalintinib + pembrolizumab
Receives: Drug: Zanzalintinib; Biological: Pembrolizumab
Zanzalintinib-Matched Placebo + PembrolizumabPlacebo comparatorSubjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab
Receives: Drug: Zanzalintinib-matched Placebo; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)

    Defined as the time from randomization to the earlier of either radiographic progressive disease (PD) per RECIST 1.1 as determined by the BICR or death from any cause

    Measured: Approximately 33 months after the first subject is randomized

  2. Overall Survival (OS)

    Defined as the time from randomization to death due to any cause

    Measured: Approximately 50 months after the first subject is randomized

Secondary outcomes (3)

  1. PFS per RECIST 1.1 by Investigator

    Defined as the time from randomization to the earlier of either radiographic PD per RECIST 1.1 as determined by the Investigator or death from any cause

    Measured: Approximately 33 months after the first subject is randomized

  2. Objective Response Rate (ORR) per RECIST 1.1 by the BICR and Investigator

    Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 as determined by the BICR and Investigator

    Measured: Approximately 33 months after the first subject is randomized

  3. Duration of Response (DOR) Per RECIST 1.1 by BICR and Investigator

    Defined as the time from the first documentation of objective response (subsequently confirmed at a visit ≥ 28 days later) to disease progression or death due to any cause

    Measured: Approximately 33 months after the first subject is randomized

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2023
  2. Study start7 Jun 2024
  3. Primary completionAug 2028 (estimated)
  4. Study completionMar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06082167
Sponsor's protocol ID
XL092-305; KEYNOTE-G06
Other IDs
EU CTR: 2023-506308-24-00, KEYNOTE-G06, MK-3475-G06
Acronym
STELLAR-305
Status last verified
Aug 2025
First submitted
9 Oct 2023
Last updated
17 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Saba NF, Harrington K, Licitra L, Machiels JP, He C, Jew T, Andrianov V, Haddad R. STELLAR-305: phase II/III study of zanzalintinib plus pembrolizumab versus pembrolizumab alone in patients with HNSCC. Future Oncol. 2025 May;21(11):1349-1356. doi: 10.1080/14796694.2025.2485015. Epub 2025 Apr 18.

    PubMed 40248950

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Zanzalintinib and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Exelixis at 168 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 168 sites in Brazil, United States, France, South Korea, Spain and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) (time frame: Approximately 33 months after the first subject is randomized). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06082167, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.

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