Symbiotic-GI-13, A Study to Learn About the Study Medicine Called PF-08634404 as Monotherapy and Combination Therapy in Adult Participants with Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2025-523525-17-00

ClinicalTrials.gov

NCT07227012

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

Phase 1b (Safety Run-In): To evaluate the safety and tolerability of PF-08634404 in combination with ipilimumab

Phase 2 (Dose Optimization/Expansion): •To evaluate the antitumor efficacy of PF-08634404 alone and in combination with ipilimumab
•To evaluate the safety and tolerability of PF-08634404 alone and in combination with ipilimumab.
•To identify a recommended dose of PF-08634404 in combination with ipilimumab.

Secondary objectives 8

1. Phase 1b (Safety Run-In): To evaluate the antitumor efficacy of PF-08634404 in combination with ipilimumab
2. To evaluate additional measurements of safety of PF-08634404 in combination with ipilimumab
3. To evaluate the PK of PF-08634404 in combination with ipilimumab
4. To evaluate the immunogenicity of PF-08634404 in combination with ipilimumab
5. Phase 2 (Dose Optimization/Expansion): To evaluate additional measurements of efficacy for PF-08634404 alone and in combination with ipilimumab
6. To evaluate additional measurements of safety of PF-08634404 alone and in combination with ipilimumab
7. To evaluate the PK of PF-08634404 alone and in combination with ipilimumab
8. To evaluate the immunogenicity of PF-08634404 alone and in combination with ipilimumab

Conditions and MedDRA coding

Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma

Regulatory references

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.
2. 2. Participants must meet the following criteria: a) Locally advanced or metastatic HCC with diagnosis confirmed by histology/ cytology or clinically by AASLD35 criteria (for patients with cirrhosis). Participants without cirrhosis require histological confirmation of diagnosis. b) Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies. For participants who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan for the current study.
3. 3. Participants must have at least 1 measurable (as defined by RECIST 1.1 per investigator) and untreated lesion.
4. 4. Have sufficient tumor tissue available, either paraffin block or slides from a core or excisional biopsy (cytology samples including cell blocks prepared from FNA biopsies and biopsies containing bone, are not adequate).
5. 5. No prior systemic therapy for HCC.
6. 6. ECOG PS score of 0 or 1.
7. 7. Child-Pugh Class - (see Appendix 9 Section 10.9.1).
8. 8. Adequate organ function determined by meeting the following criteria: a) Participants must meet the hematologic criteria below without the use of transfusions or growth factors (platelet or red blood cell transfusions, TPO, EPO, G-CSF, IL-11, etc.) within 7 days prior to baseline laboratory tests.
9. 9. Participants with HBV infection (as characterized by positive HBsAg or detectable HBV DNA) must be treated with antiviral therapy, per institutional practice, to ensure adequate viral suppression (HBV DNA ≤500 IU/mL) prior to enrollment. Note: HBV-positive participants must remain on antiviral therapy for the study duration.
10. 10. Participants with HCV infection (as characterized by the presence of detectable anti-HCV antibody and detectable HCV RNA) must be managed per local institutional practice.
11. 11. The participant must provide written informed consent.

Exclusion criteria 22

1. 1. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. 2. Participants with any of the following: a) - b) - Note: Participants must undergo an EGD, and all sizes of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Participants who have undergone an EGD within 6 months prior to initiation of study treatment do not need to repeat the procedure. c) Moderate or severe ascites d) Active or history of hepatic encephalopathy within 6 months prior to the first dose.
3. 3. Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be enrolled if all of the following are met: a) CNS metastases have been clinically stable with no evidence of clinical or radiographic disease progression for ≥14 days after completion of definitive radiotherapy and/or surgery and prior to study intervention. b) The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention. c) Participants with asymptomatic brain metastases of longest diameter <1 cm permitted if all the following criteria are met:  absence of neurological symptoms,  no need for corticosteroids, and  brain metastasis has no evidence of edema or hemorrhagic features
4. 4. Clinically significant risk of hemorrhage or fistula including but not limited to the following:  Significant tumor necrosis or cavitation,  The investigator deems that participation in the study poses a risk of hemorrhage;  Tumor invasion or compression of surrounding critical organs (such as aorta, heart and pericardium, superior vena cava, trachea, and esophagus) or a risk of developing tracheoesophageal or pleuroesophageal fistula;  Mediastinal lymph node metastasis with invasion of the trachea or main bronchi. If centrally located mediastinal masses (<30 mm from the carina) identified by CT scan or chest x-ray, CT scan with intravenous contrast or MRI within 21 days prior to randomization must exclude major airway or blood vessel invasion by tumor.
5. 5. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
6. 6. Unresolved toxicities from prior antitumor therapy, defined as not having recovered to NCI CTCAE v5.0 Grade 0 or 1, or to levels specified in the inclusion/exclusion criteria, with the exception of alopecia. Participants who experience irreversible toxicity that is not expected to worsen with continued administration of the study intervention (eg, hearing loss) may be enrolled in the study after consultation with the medical monitor. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study after consultation with the medical monitor.
7. 7. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
8. 8. Participants with active autoimmune diseases requiring systemic treatment within the past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs) a) Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is allowed. b) Participants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per Exclusion Criterion #10), or resolved childhood asthma/atopy are allowed. c) Participants requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections are allowed. d) Participants with Sjögren’s syndrome are allowed.
9. 9. Evidence of non-infectious or drug-induced ILD or pneumonitis that:  Was previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks  Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or;  Is currently diagnosed and managed with systemic therapy, or  Is suspected on radiologic imaging at screen
10. 10. Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to first dose including but not limited to the following: a) Unstable angina b) Myocardial infarction c) Uncontrolled or significant arrhythmia (including sustained ventricular tachyarrhythmia and ventricular fibrillation), untreated serious conduction system abnormalities (eg, bifascicular block [defined as right bundle branch and left anterior or posterior hemiblock], 3rd degree AV block) d) Coronary/peripheral artery bypass graft e) Transient ischemic attack, cerebrovascular accident, cerebral infarction (excluding lacunar infarction), or cerebral hemorrhage f) Symptomatic congestive heart failure or symptoms consistent with NYHA Functional Class II or higher g) Decompensated liver cirrhosis h) Nephrotic syndrome i) Uncontrolled diabetes defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained (or poor compliance with hypoglycemic medications) j) Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, or poor compliance with antihypertensive medications) k) Arterial thromboembolic event or Grade ≥3 venous thromboembolic eventas specified in CTCAE 5.0. l) Hypertensive crisis m) Hypertensive encephalopathy n) Baseline QTcF interval >480 msec. If QTcF exceeds 480 msec, the ECG is to be repeated twice and the average of the 3 QTcF values should be used to determine the participant’s eligibility. Computer-interpreted ECGs with abnormal findings should be overread by an investigator physician experienced in reading ECGs before excluding participants.
11. 11. Major surgery or severe trauma within 4 weeks prior to the first dose or planned major surgery during the study; minor local surgery (excluding peripherally inserted central catheter placement and implantable central venous port placement) within 3 days prior to the first dose. Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting study intervention.
12. 12. History of severe bleeding tendency or coagulation dysfunction, such as presence of clinically significant bleeding symptoms within 1 month prior to the first dose, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or expectorating ≥1/2 teaspoon of fresh blood or small blood clots or coughing up blood without sputum; participants with blood-streaked sputum are allowed to be enrolled), or epistaxis (excluding minor nosebleeds and blood-tinged nasal discharge).
13. 13. History of severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding, including bleeding event due to esophageal and/or gastric varices, within 6 months prior to the first dose.
14. 14. Participants with acute, chronic or symptomatic infections including: a) Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of administration of first dose of study intervention (other than for HIV, HBV or HCV treatment). Routine antimicrobial prophylaxis is permitted. b) Known seropositivity of HIV, except for participants with controlled HIV infection on a stable regimen of ART (CD4+ count >200/mm3 and viral load of <400 copies/mL). The investigator will ensure the ART does not result in substantial interactions with study or concomitant medications. Note: All participants will be tested for HIV locally prior to randomization and if not in contradiction with local legislation. c) Participants with known active TB. Participants suspected of active TB are required to undergo clinical evaluation to rule out the condition.
15. 15. Participants with history of primary immunodeficiency.
16. 16. Known to have a history of a severe allergy to any component of the study intervention, or a history of severe allergic reaction to chimeric or humanized antibody.
17. 17. Previous treatment with anti-VEGF inhibitor or immunotherapy, including but not limited to immune checkpoint inhibitors (eg, PD-(L)-1 antibodies, anti-CTLA-4 antibodies).
18. 18. Prior radiotherapy to a non-liver region ≤2 weeks of first dose of study intervention.
19. 19. Other Prior/Concomitant Therapies: a) Use of therapeutic oral or parenteral anticoagulants or thrombolytic agents within 10 days prior to the first dose of study intervention (excluding prophylactic use). Prophylactic use of low molecular weight heparin is permitted. b) Use of chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole, clopidogrel, or similar agents within 10 days prior to the first dose of study intervention. Once daily low-dose aspirin (≤100 mg/day) is permitted. c) Use of any live or attenuated live vaccine within 4 weeks prior to the first dose of study intervention, or planned vaccination of any live or attenuated live vaccine during the study d) Current use of a high-dose systemic corticosteroids (>10 mg daily prednisone or equivalent) or other immune suppressant or has a condition requiring a chronic highdose steroid or immune suppressant. e) Use of any prohibited concomitant medication(s) within 21 days of the first dose of study intervention or unwillingness or inability to use a required concomitant medication(s). Refer to Section 6.9 for additional details.
20. 20. Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
21. 21. Investigator site staff directly involved in the conduct of the study and their family members, site staff, otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
22. 22. Breastfeeding female participants, individuals of childbearing potential, and male participants who are unwilling to follow pregnancy measures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase 1b (Safety Run-In): AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
2. DLTs
3. Phase 2 (Dose Optimization/Expansion): Confirmed ORR per RECIST 1.1 by investigator.
4. AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.

Secondary endpoints 13

1. Phase 1b (Safety Run-In): Confirmed ORR per RECIST 1.1 by investigator
2. DOR per RECIST 1.1 by investigator
3. PFS per RECIST 1.1 by investigator
4. OS
5. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
6. Predose and/or postdose concentrations of PF-08634404
7. Incidence of ADA against PF-08634404
8. Phase 2 (Dose Optimization/Expansion): DOR per RECIST 1.1 by investigator
9. PFS per RECIST 1.1 by investigator
10. OS
11. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
12. Predose and/or postdose concentrations of PF-08634404.
13. Incidence of ADA against PF-08634404.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 6

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Results and documents

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

Documents 37 files

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

Application history

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