PF-08634404 for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Participants of childbearing potential (Section 10.4.3) must have a negative serum pregnancy test (minimum sensitivity 25 mIU/mL or equivalent quantitative assay) result within 72 hours prior to the first dose of study treatment. Participants with false positive results and documented verification that the participant is not pregnant are eligible for participation.\n- The participant must provide informed consent.\n- Histological or cytological confirmed colorectal adenocarcinoma.\n- Evidence of Stage IV metastatic disease.\n- Known RAS mutation status per local test (CCI). Participants with unknown RAS status despite attempt to test are eligible for participation.\n- No prior systemic therapy for metastatic disease. Note: Participants with early-stage disease who received prior systemic neoadjuvant or adjuvant chemotherapy and present with reoccurrence/metastatic disease within 6 months of stopping treatment will count as having prior therapy in the metastatic setting and are not eligible.\n- ECOG performance status 0-1.\n- At least one measurable lesion according to RECIST 1.1 per Investigator assessment. Participants with prior definitive radiotherapy must have measurable disease per RECIST 1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions.\n- Have tumor tissue available, either paraffin block or slides from a core, or excisional biopsy (FNA cell blocks, cytology samples and biopsies containing bone are not adequate). a.\tSee Central Laboratory Manual for tissue specifications, handling, and shipping instructions. b.\tIf less than the required amount of slides as outlined in the laboratory manual are available, the sponsor must be contacted to determine if available slides are sufficient. c.\tIf sufficient archival tissue is not available, a new baseline tumor biopsy with adequate tissue is required, unless medically infeasible and with prior agreement with the medical monitor and documentation submitted to the sponsor.\n- Adequate hematologic, hepatic, and renal function by meeting the following criteria a.\tParticipants 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 screening laboratory tests."}

Exclusion criteria

• {"criterion_text":"- Locally confirmed BRAF V600E mutation\n- Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to first dose including but not limited to the following: a.\tUnstable angina b.\tMyocardial infarction c.\tUncontrolled 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.\tCoronary/peripheral artery bypass graft e.\tTransient ischemic attack, cerebrovascular accident, cerebral infarction (excluding lacunar infarction), or cerebral hemorrhage f.\tSymptomatic congestive heart failure or symptoms consistent with NYHA Functional Class II or higher g.\tBaseline QTcF interval > 480 msec •\tIf 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. h.\tDecompensated liver cirrhosis i.\tNephrotic syndrome j.\tUncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, or poor compliance with antihypertensive medications) k.\tArterial thromboembolic event and venous thromboembolic event Grade ≥3 as specified in CTCAE 5.0 l.\tHypertensive crisis m.\tHypertensive encephalopathy\n- 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.\tReplacement 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.\tParticipants with vitiligo, psoriasis, type 1 diabetes mellitus (if not excluded per exclusion criterion 11), or resolved childhood asthma/atopy are allowed. c.\tParticipants with Sjögren’s syndrome are allowed.\n- Evidence of non-infectious or drug-induced ILD pneumonitis that: •\tWas previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks, or; •\tHad onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or; •\tIs currently diagnosed and managed with systemic therapy, or; •\tIs suspected on radiologic imaging at screening.\n- Unresolved toxicities from prior anti-tumor therapy, that did not recover 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.\n- Grade ≥3 baseline neuropathy, or ongoing residual Grade ≥2 neuropathy from prior oxaliplatin.\n- History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.\n- 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. Participants with a history of other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after consultation with sponsor or designee.\n- Known or suspected hypersensitivity to any component of study intervention or their excipients at the planned doses.\n- Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.\n- Locally confirmed MSI-high or dMMR colorectal cancer\n- Participants with known active symptomatic CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression Note: Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be enrolled if all of the following are met: a.\tCNS 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.\tThe participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention.\n- Known DPD deficiency (refer to the local 5-FU label or local clinical guidance for DPD status recommendation prior to starting treatment).\n- Clinically significant risk of hemorrhage or fistula including but not limited to the following: a.\tSignificant tumor necrosis or cavitation b.\tThe investigator deems that participation in the study poses a risk of hemorrhage; c.\tTumor 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 d.\tMediastinal 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.\n- 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.\n- History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n- Any Grade ≥3 bleeding/hemorrhage events within 28 days of Cycle 1 Day 1, or prior history of clinically significant bleeding events, including unhealed wounds following surgical procedure.\n- Participants with acute, chronic or symptomatic infections including: a.\tCurrently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted. b.\tKnown 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. c.\tKnown active HBV infection by positive HBV surface antigen. d.\tActive HCV infection (positive HCV viral load by PCR). Participants who have been treated for HCV infection are eligible if they have documented sustained virologic response 12 weeks after completion of antiviral therapy. Note: Testing for HIV, HBV, or HCV is not required unless mandated by local health authorities. e.\tParticipants with known active TB infection •\tParticipants suspected to have active TB are required to undergo clinical evaluation to rule out the condition."}

Primary endpoints

• {"endpoint_text":"- PFS by BICR","definition_or_measurement_approach":"Progression-free survival assessed by Blinded Independent Central Review (BICR); progression assessment uses RECIST 1.1 criteria as referenced in the protocol."}
• {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}

Secondary endpoints

• {"endpoint_text":"- •\tPFS by investigator •\tORR by BICR and by investigator •\tDOR by BICR and by investigator •\tPFS2 (PFS after next-line therapy) by investigator","definition_or_measurement_approach":"Efficacy measures assessed by investigator and by BICR; RECIST 1.1 used for tumor response assessments where applicable."}
• {"endpoint_text":"- •\tAEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study intervention. •\tLaboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing.","definition_or_measurement_approach":"Safety assessed by adverse event reporting and laboratory abnormalities graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- •\tPredose and postdose concentrations of PF-08634404","definition_or_measurement_approach":"PK sampling for PF-08634404 predose and postdose concentrations."}
• {"endpoint_text":"- •\tIncidence of ADA against PF-08634404","definition_or_measurement_approach":"Immunogenicity assessed by measuring anti-drug antibodies (ADA) incidence against PF-08634404."}
• {"endpoint_text":"- •\tMean score change from baseline in participant reported GHS/QoL, function, and symptoms per EORTC QLQ-C30 •\tMean score change from baseline in participant reported function and symptoms scales per EORTC QLQ-CR29","definition_or_measurement_approach":"Patient-reported outcomes measured using EORTC QLQ-C30 and EORTC QLQ-CR29 instruments; mean change from baseline recorded."}
• {"endpoint_text":"- •\tTime to definitive deterioration in participant reported GHS/QoL, function and symptoms per EORTC QLQ-C30 •\tTime to definitive deterioration in participant reported function and symptoms per EORTC QLQ-CR29","definition_or_measurement_approach":"Time-to-event analysis for definitive deterioration in PRO measures according to EORTC QLQ-C30 and QLQ-CR29."}

Methods

• Use of country-specific recruitment arrangements (K1 documents) and study brochures (K2) — country-specific K1/K2 materials present for BE, DK, FR, DE, IT, ES, NL, PL.
• Global participant website and global participant website layout (digital recruitment) documented.
• Global Facebook page and other social media outreach (Global Facebook Page document) for participant outreach.
• Participant outreach image library and participant media board used for recruitment materials.
• Study brochures, 'About Clinical Trials' fact sheets and local-language recruitment materials for targeting potential participants and clinicians.
• Third-party vendors contracted for patient recruitment and retention (Innovative Trials Limited, Continuum Clinical LLC, Omnitrace Corp., Center For Information And Study On Clinical Research Participation Inc., and others).

Belgium

Earliest CTIS Part Ii Submission Date

16-10-2025

Latest Decision Or Authorization Date

26-03-2026

Processing Time Days

161

Number Of Sites

4

Number Of Participants

15

Denmark

Earliest CTIS Part Ii Submission Date

12-03-2026

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

11

Number Of Sites

4

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

12-01-2026

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

77

Number Of Sites

8

Number Of Participants

30

Germany

Earliest CTIS Part Ii Submission Date

09-03-2026

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

16

Number Of Sites

10

Number Of Participants

18

Italy

Earliest CTIS Part Ii Submission Date

30-01-2026

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

54

Number Of Sites

10

Number Of Participants

54

Spain

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

32

Number Of Sites

10

Number Of Participants

63

Netherlands

Earliest CTIS Part Ii Submission Date

17-03-2026

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

6

Number Of Sites

1

Number Of Participants

5

Poland

Earliest CTIS Part Ii Submission Date

20-02-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

35

Number Of Sites

5

Number Of Participants

20

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

WCG Clinical Inc.

Responsibilities

Study Coordination Support Services

Name

IQVIA Limited

Responsibilities

Electronic CoA (eCoA) support services

Name

Cytel Inc.

Responsibilities

EDMC Statistical Analysis

Name

PAREXEL International

Responsibilities

IMP & Clinical Supplies Destruction

Name

Icon Development Solutions LLC

Name

Bioclinica Inc.

Third parties

• {"country":"United Kingdom","full_name":"Innovative Trials Limited","duties_or_roles":"Patient Recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Study Coordination Support Services","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Electronic CoA (eCoA) support services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"EDMC Statistical Analysis","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Recruitment and Retention","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PAREXEL International","duties_or_roles":"IMP & Clinical Supplies Destruction","organisation_type":"Industry"}
• {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"Patient recruitment","organisation_type":"Patient organisation/association"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Continuum Clinical LLC","duties_or_roles":"Patient recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}