Clinical trial NCT06448364: A Study in Advanced/Metastatic Solid Tumors With the Study Medicine (PF-07329640) When Given Alone or In Combination
Official title: FIRST-IN-HUMAN (FIH), OPEN-LABEL, PHASE 1 DOSE ESCALATION AND EXPANSION STUDY DESIGNED TO EVALUATE THE SAFETY, TOLERABILITY, PK, PD, AND PRELIMINARY CLINICAL ACTIVITY OF PF-07329640 AS A SINGLE AGENT OR IN COMBINATION TREATMENT FOR PARTICIPANTS WITH ADVANCED SOLID TUMORS.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Non-Small Cell Lung Cancer
Colorectal Cancer
Urothelial Cancer
Melanoma
Keywords: Solid tumors
metastatic
advanced
micro satellite stable
anti-VEG
anti-PD-1
PF-07329640
LTbetaR
LTbR
sasanlimab
bevacizumab
PD-1 resistance
PD-1 naive
PDx resistance
PDxnaive
Carcinoma, Non-Small Cell Lung
Non-Small Cell Lung Cancer
Non-Small Cell Lung Carcinoma
Non-Small-Cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Non-Muscle Invasive Bladder Cancer (NMIBC)
Non-Muscle-Invasive Bladder Cancer
Malignant Melanoma
Microsatellite Stable Colorectal Cancer (MSS CRC)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-06-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: PART 1: Number of participants with Dose-limiting toxicities (DLT)
timeFrame: First cycle, Day 1 up to Day 28
measure: PART 1 & 2: Incidence of Adverse Events (AE)s
timeFrame: From start of the treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
measure: To: PART 1 & 2: Number of participants with laboratory abnormalities
timeFrame: From start of treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
measure: Part 2: "Objective Response - Number of Participants With Objective Response "
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'
Secondary outcomes:
measure: Part 1: Objective Response - Number of Participants With Objective Response
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
measure: Time to event endpoints: duration of response (DOR) by RECIST v1.1
timeFrame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt
measure: Time to event endpoints: progression-free survival (PFS) by RECIST v1.1
timeFrame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt
measure: Part 1A: Maximum Observed Serum Concentration (Cmax) of PF-07329640
timeFrame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
measure: Part 1A: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07329640
timeFrame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
measure: Part 1A: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07329640
timeFrame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
measure: Serum Concentrations of PF-07329640 in combination (Part 1B/1C/2A/2B/2C)
timeFrame: pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1Day 15, Cycle 2 Day 1 (Each cycle is 28 days)
measure: Incidence and titers of antidrug antibodies (ADA) against PF-07329640
timeFrame: Baseline though study completion, an average of 2 years
measure: Paired Tumor Biopsies
timeFrame: Baseline through Cycle 2 Day 15 (each cycle is 28 days)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Rio Piedras
country: Puerto Rico
facility: Hospital Oncológico Dr. Isaac González-Martinez
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials- Hospital Oncologico
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: