A Study in Advanced/Metastatic Solid Tumors With the Study Medicine (PF-07329640) When Given Alone or In Combination

NCT ID: NCT06448364

Last Updated: 2024-11-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-09
• Study Completion Date: 2024-08-15

Brief Summary

The purpose of this study is to learn about the safety (the impact of the study drug on the participant's body), effects of the study drug alone or in combination with bevacizumab or sasanlimab, and to find the best dose.

This study is seeking participants who have solid tumors that:

• have advanced (cancer that doesn't disappear or stay away with treatment) or
• has spread to other parts of the body (metastatic).

This includes (but limited to) the following cancer types:

• Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.
• Colorectal Cancer (CRC): This is a disease where cells in the colon or rectum grow out of control.
• Urothelial Cancer (UC): This is a cancer that starts in the urinary systems.
• Melanoma: Skin cancer that develops when melanocytes (the cells that give the skin its tan or brown color) start to grow out of control.

All participants in this study will receive the study medication (PF-07329640) as an IV infusion (given directly into a vein) at the study clinic every week for repeating 28-day cycles.

Depending on which part of the study participants are enrolled in they will receive the study medication (PF-07329640 alone or in combination with other anti-cancer medications (bevacizumab or sasanlimab). Bevacizumab is given in the clinic as IV infusion every two weeks and sasanlimab is given as a shot under the skin every 4 weeks.

Participants can continue to take the study medication (PF-07329640) and bevacizumab until their cancer is no longer responding. Participants who are taking sasanlimab may receive it for up to 2 years.

The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.

Participants will be involved in this study for up to 4 years. During this time, they will have a study visit every week. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.

Conditions

Advanced or Metastatic Solid Tumors; Non-Small Cell Lung Cancer; Colorectal Cancer; Urothelial Cancer; Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A: PF-07329640 (αLTβR) Monotherapy

PF-07329640 (αLTβR) monotherapy at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

Part 1B: PF-07329640 (αLTβR) + bevacizumab

PF-07329640 (αLTβR) + bevacizumab dose escalation in NSCLC and MSS CRC at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

bevacizumab

Intervention Type: BIOLOGICAL

a monoclonal antibody that blocks VEGF

Part 1C: PF-07329640 (αLTβR) + sasanlimab

PF-07329640 (αLTβR) + sasanlimab dose escalation in NSCLC, melanoma, UC, and MSS CRC at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

sasanlimab

Intervention Type: BIOLOGICAL

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Part 2A: PF-07329640 (αLTβR) + bevacizumab

PF-07329640 (αLTβR) + bevacizumab dose expansion in NSCLC 2L+ and MSS CRC 2L+ at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

bevacizumab

Intervention Type: BIOLOGICAL

a monoclonal antibody that blocks VEGF

Part 2B: PF-07329640 (αLTβR) + sasanlimab

PF-07329640 (αLTβR) + sasanlimab dose expansion in NSCLC, melanoma, UC, and MSS CRC at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

sasanlimab

Intervention Type: BIOLOGICAL

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Part 2C: PF-07329640 (αLTβR) + SOC

PF-07329640 (αLTβR) + SOC (anti-PD-1+ platinum-based chemo) dose expansion for αPDx-naïve NSCLC 1L at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

Part 2D: PF-07329640 (αLTβR)

PF-07329640 (αLTβR) dose expansion in advanced solid tumors at prescribed dose and frequency in 28-day cycles

Group Type: EXPERIMENTAL

PF-07329640

Intervention Type: BIOLOGICAL

an anti-lymphotoxin beta receptor agonist

Interventions

PF-07329640

an anti-lymphotoxin beta receptor agonist

Intervention Type: BIOLOGICAL

sasanlimab

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Intervention Type: BIOLOGICAL

bevacizumab

a monoclonal antibody that blocks VEGF

Intervention Type: BIOLOGICAL

Other Intervention Names

LtbR, LTbetaR; PF-06801591; Zirabev; Bevacizumab-bvzr

Eligibility Criteria

Inclusion Criteria

• Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor
• Part 1:

• Part 1A: Participants with solid tumors where anti-PD-(L)1 is an established treatment. Participants must have progressed on or following prior anti-PD-(L)1 therapy if approved, available, tolerable, and eligible.
• Part 1B & C: Participants either meeting Part 1A criterion, or participants with "cold" solid tumors where anti-PD-(L)1 therapy is not an established treatment
• Part 2:

• Part 2A:
• Cohort 1: Participants with NSCLC must have received platinum-based chemotherapy and anti-PD-(L)1 or have intolerability to or refusal of standard therapies. NSCLC participants with known activating mutation(s) must also have received prior approved and available targeted therapy(ies) for the associated mutation(s) or have intolerability or documented refusal of these therapies.
• Cohort 2: Participants with MSS CRC must have received at least fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy, an anti-VEGF agent (if not receiving anti-VEGF on protocol), and anti-epidermal growth factor receptor (EGFR) inhibitor (if RAS wildtype) and/or other molecularly targeted therapy if appropriate.
• Part 2B:

• NSCLC (2L+) participants as described above in Part 2A
• MSS CRC (2L+) participants as described above in Part 2A
• UC (2L+) participants must have received prior platinum-based chemotherapy, anti-PD-(L)1 therapy, or enfortumab vedotin.
• Part 2C; anti-PDx naive NSCLC (1L) participants must not have received standard of care therapy with anti-PD-(L)1.
• At least 1 measurable lesion based on RECIST 1.1 that has not been previously irradiated (Part 1 exceptions permitted after review and approval)
• Able to provide pre-treatment (and optional on-treatment) tumor tissue
• Resolution of acute effects of any prior therapy to either baseline or CTCAE Grade 1

Exclusion Criteria

• Treatment with any systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to planned first dose
• Prior treatment with another anti-LTβR agonist
• Systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas). Prior targeted or endocrine therapy require an interval of 2 weeks or 5 half-lives (whichever is shorter) prior to planned first dose.
• Lack of adequate organ (bone marrow, renal, liver) function
• Active infection requiring systemic treatment.
• Active or history of autoimmune disease (eg, systemic lupus erythematosus, rheumatoid arthritis) requiring chronic systemic steroid or immune-modulatory therapy (not including oral physiological replacements)
• History of Grade ≥3 immune mediated adverse event (AE) (including aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations that were considered drug related) and/or CRS that was considered related to prior immune-modulatory therapy and required immunosuppressive therapy.
• Known or suspected hypersensitivity to any PF-07329640 components, or to monoclonal antibodies (mAbs) or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukin, or anti-PD-(L)1 therapy (the latter applicable for Part 1C and Part 2B/C participants only
• Brain metastasis or primary brain tumor requiring immediate local intervention (surgery, radiosurgery) in the opinion of the investigator.
• Other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease. Presence of other indolent cancer requires prior sponsor approval.
• Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant.
• Pregnant or breastfeeding
• Persistent or recurring ≥ Grade 2 neuropathy prior to study entry

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Highlands Oncology

Fayetteville, Arkansas, United States

Highlands Oncology

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

NEXT Oncology

San Antonio, Texas, United States

Hospital Oncológico Dr. Isaac González-Martinez

Rio Piedras, , Puerto Rico

Pan American Center for Oncology Trials, LLC

Rio Piedras, , Puerto Rico

Pan American Center for Oncology Trials- Hospital Oncologico

Rio Piedras, , Puerto Rico

Countries

United States; Puerto Rico

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=C5181001

To obtain contact information for a study center near you, click here.

Other Identifiers

C5181001

Identifier Type: -

Identifier Source: org_study_id