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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Colorectal Cancer; Non-Small Cell Lung Cancer; Urothelial Cancer; Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Biological: PF-07329640; Biological: bevacizumab; Biological: sasanlimab

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials- Hospital Oncologico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials, LLC
  • Rio Piedras, Puerto Rico, 00935
    • Hospital Oncologico Dr. Isaac Gonzalez-Martinez
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • Texas
    • San Antonio, Texas, United States, 78229
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A: PF-07329640 (αLTβR) Monotherapy; PF-07329640 (αLTβR) monotherapy at prescribed dose and frequency in 28-day cycles	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR
Experimental: 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	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR; Biological: bevacizumab; a monoclonal antibody that blocks VEGF; Other Names: Zirabev; Bevacizumab-bvzr
Experimental: 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	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR; Biological: sasanlimab; A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2; Other Names: PF-06801591
Experimental: 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	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR; Biological: bevacizumab; a monoclonal antibody that blocks VEGF; Other Names: Zirabev; Bevacizumab-bvzr
Experimental: 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	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR; Biological: sasanlimab; A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2; Other Names: PF-06801591
Experimental: 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	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR
Experimental: Part 2D: PF-07329640 (αLTβR); PF-07329640 (αLTβR) dose expansion in advanced solid tumors at prescribed dose and frequency in 28-day cycles	Biological: PF-07329640; an anti-lymphotoxin beta receptor agonist; Other Names: LtbR, LTbetaR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PART 1: Number of participants with Dose-limiting toxicities (DLT)	Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes:	First cycle, Day 1 up to Day 28
PART 1 & 2: Incidence of Adverse Events (AE)s	An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.	From start of the treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
To: PART 1 & 2: Number of participants with laboratory abnormalities	Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).	From start of treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
Part 2: "Objective Response - Number of Participants With Objective Response "	Percentage of participants with objective response-based best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator.	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective Response - Number of Participants With Objective Response	Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
Part 1A: Maximum Observed Serum Concentration (Cmax) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Part 1A: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Part 1A: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, EOI, 4 hours post-dose (Day 8); pre-dose, EOI (Day 15) Cycle 2: Pre-dose, EOI, 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, and 4 hours post-dose (Day 15)	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Serum Concentrations of PF-07329640 in combination (Part 1B/1C/2A/2B/2C)	comparison Predose and end of infusion blood serum concentrations at Cycle 1 day 1 and 15, and Cycle Day 1	pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1Day 15, Cycle 2 Day 1 (Each cycle is 28 days)
Incidence and titers of antidrug antibodies (ADA) against PF-07329640	the number of patients with ADAs against PF-07329640 and the concentration of those ADAs	Baseline though study completion, an average of 2 years
Paired Tumor Biopsies	Changes in quantity and maturation state of tertiary lymphoid structure (TLS)s in tumor biopsy tissues at Cycle 2 Day 15	Baseline through Cycle 2 Day 15 (each cycle is 28 days)
Time to event endpoints: duration of response (DOR) by RECIST v1.1	Time to event: DOR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.	Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt
Time to event endpoints: progression-free survival (PFS) by RECIST v1.1	Time to event: PFS according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.	Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2024
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): August 15, 2024

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 7, 2024

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Solid tumors; bevacizumab; Colorectal Cancer; metastatic; advanced; Colorectal Carcinoma; anti-PD-1; Non-Small Cell Lung Carcinoma; Malignant Melanoma; Colorectal Tumors; Neoplasms, Colorectal; Non-Small-Cell Lung Carcinoma; Nonsmall Cell Lung Cancer; Carcinoma, Non-Small Cell Lung; Non-Muscle Invasive Bladder Cancer (NMIBC); sasanlimab; Non-Muscle-Invasive Bladder Cancer; PD-1 resistance; micro satellite stable; anti-VEG; PF-07329640; LTbetaR; LTbR; PD-1 naive; PDx resistance; PDxnaive; Microsatellite Stable Colorectal Cancer (MSS CRC)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: C5181001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No