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Study of TTI-622 in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05261490
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : January 23, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

Pegylated liposomal doxorubicin (PLD), a type of chemotherapy, is a standard treatment option for patients with platinum-resistant ovarian cancer. However, despite being consider a standard treatment option, the clinical benefit of chemotherapy alone for these patients is small. Historically, response rates for PLD monotherapy have only ranged from 12 to 35% with a high likelihood of recurrence within months after treatment initiation. Although bevacizumab (BEV), an anti-new-vascular growth monoclonal antibody has been approved by FDA to combine with standard chemotherapy (e.g., PLD) for platinum-resistant recurrent ovarian cancer, there are still many restrictions or contraindications preventing certain women from receiving bevacizumab's combination treatment. The goal of this study is to improve upon the activity of PLD in a safe manner to provide a more effective therapeutic option for this group of patients.

The purpose of this study is to assess TTI-622 administered in combination with PLD in patients with platinum-resistant ovarian cancer and for whom PLD is a reasonable treatment option. The first portion of the study will evaluate the safety of increasing dose levels of TTI-622 in combination with PLD at 40 mg/m2 in patients with platinum-resistant EOC (epithelial ovarian cancer). This is a group of cancer, including ovarian, peritoneal and fallopian tube malignancy. The aim of the first portion of the study is to establish a combination regimen for further assessment in a dose expansion cohort.

The study will consist of a 28-day screening period to ensure participants are qualified for the study treatment plan. During the treatment period, patients will receive TTI-622 in combination with PLD in 28-day cycles until their disease progresses or unacceptable toxicity develops. There will be a long-term follow-up period in this study to assess overall survival (length of time since start of treatment patients are alive).


Condition or disease Intervention/treatment Phase
Ovarian Cancer Ovarian Neoplasms Ovarian Carcinoma Fallopian Tube Cancer Epithelial Ovarian Cancer Primary Peritoneal Carcinoma Drug: TTI-622 Drug: Pegylated Liposomal Doxorubicin Phase 2

Detailed Description:

Pegylated liposomal doxorubicin (PLD) is a standard treatment option for patients with platinum-resistant ovarian cancer who are not candidates for chemotherapy in combination with bevacizumab. However, despite being consider a standard treatment option, the clinical benefit of chemotherapy for this patient population is small. The goal of this clinical trial is to improve upon the activity of PLD in a safe manner to provide a more effective therapeutic option for this group of patients.

TTI-622-02 is a multi-center, open-label study designed to evaluate TTI-622 administered in combination with PLD in patients with platinum-resistant ovarian cancer and for whom PLD is a reasonable treatment option. The first portion of the study will evaluate the safety of increasing dose levels of TTI-622 in combination with PLD at 40 mg/m2 in patients with platinum-resistant EOC, including ovarian, peritoneal and fallopian tube malignancy, and establish a combination regimen for further evaluation in a dose expansion cohort. The study will consist of a 28-day screening period, a treatment period in which patients will receive TTI-622 in combination with PLD in 28-day cycles until documentation of objective disease progression or development of unacceptable toxicity, and a long-term follow-up period to assess overall survival.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ⅰ/Ⅱ Study of TTI-622 in Combination With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer
Actual Study Start Date : August 1, 2022
Estimated Primary Completion Date : July 21, 2025
Estimated Study Completion Date : July 21, 2026


Arm Intervention/treatment
Experimental: Dose Escalation

TTI-622 will be administered with initial dose of 12 mg/kg by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles.

Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 by intravenous infusion on Day 1 of each 28-day cycle.

Drug: TTI-622
TTI-622 will be administered by intravenous infusion.

Drug: Pegylated Liposomal Doxorubicin
Pegylated Liposomal Doxorubicin will be administered by intravenous infusion.
Other Name: PLD

Experimental: Dose Expansion

TTI-622 will be administered with selected dose from the escalation phase by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles.

Pegylated Liposomal Doxorubicin 40 mg/m^2 by intravenous infusion on Day 1 of each 28-day cycle

Drug: TTI-622
TTI-622 will be administered by intravenous infusion.

Drug: Pegylated Liposomal Doxorubicin
Pegylated Liposomal Doxorubicin will be administered by intravenous infusion.
Other Name: PLD




Primary Outcome Measures :
  1. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 Pegylated Liposomal Doxorubicin (PLD) in 28-day cycles in escalation phase; type of adverse events [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the type of adverse events.

  2. Identify the Recommended Phase 2 Dose from the Escalation Phase [ Time Frame: First dose date up to 1 year ]
    Determine Phase 2 Dose for Expansion Phase

  3. Assess clinical activity of TTI-622 maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D) in combination with PLD in the Expansion Phase overall response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) . [ Time Frame: First dose date up to 3 years ]
    Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the overall response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  4. Percentage of patients experiencing adverse events [ Time Frame: First dose date up to 3 years ]
    Percentage of patients who reported adverse events while on study

  5. Percentage of patients with objective response [ Time Frame: Up to 3 years ]
    Evaluation the percentage of patients with objective response (complete response [CR] + partial response [PR]) as defined by RECIST v 1.1 criteria.

  6. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; frequency of adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the frequency of adverse events.

  7. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; severity of adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the severity of adverse events

  8. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; timing of adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the timing of adverse events.

  9. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; causal relationship of adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the causal relationship of adverse events.

  10. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in vitals signs. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the number of events with changes from baseline in vital signs.

  11. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in laboratory assessments. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by number of events with changes from baseline in laboratory assessments.

  12. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; by treatment delays. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by treatment delays .

  13. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; by discontinuations. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by discontinuations.

  14. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in Electrocardiogram (ECG) findings. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by the number of events with changes from baseline in Electrocardiogram (ECG) findings.

  15. Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the other markers of clinical benefit . [ Time Frame: First dose date up to 3 years ]
    Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the other markers of clinical benefit as defined by irRECIST criteria.

  16. Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the disease control rate. [ Time Frame: First dose date up to 3 years ]
    Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the disease control rate[complete response + partial response + stable disease]) (DCR [CR + PR + SD]) as defined by RECIST v1.1 criteria.

  17. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; treatment emergent adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by treatment emergent adverse events.

  18. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; serious adverse events. [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by serious adverse events.

  19. Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; established MTD [ Time Frame: First dose date up to 3 years ]
    Characterize the overall safety profile as assessed by established MTD.

  20. Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the immune-related Response Evaluation Criteria in Solid Tumors. [ Time Frame: First dose date up to 3 years ]
    Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria.


Secondary Outcome Measures :
  1. Duration of progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    Characterize progression-free survival (PFS) as defined by RECIST v1.1 criteria

  2. Overall Survival (OS) [ Time Frame: Up to 3 years ]
    The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.

  3. Duration of response [ Time Frame: Up to 3 years ]
    Characterize duration of response (DOR) as defined by RECIST v1.1 criteria.

  4. Time to progression and new metastases [ Time Frame: First dose date up to 3 years ]
    The length of time to progression or new metastases

  5. Time to worsening of Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: First dose date up to 3 years ]
    The length of time to worsening of performance status



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Histologically-confirmed epithelial ovarian cancer (EOC), fallopian tube carcinoma (FTC) or primary peritoneal carcinomas (PPC).
  • Platinum-resistant disease (progression ≥1 month and ≤6 months after a minimum of four cycles of last platinum-based treatment)
  • Progression with standard of care therapies, including platinum-based therapies, poly ADP ribose polymerase (PARP) inhibitors or bevacizumab in the platinum-sensitive setting or intolerability to such therapies or patient refusal
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Adequate organ and hematologic function
  • No more than four prior treatment regimens for platinum-resistant disease
  • All adverse events from prior treatment must be the Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.

Key Exclusion Criteria:

  • Platinum-refractory disease (defined as progression on or within 3 months of completing primary first-line platinum-based treatment)
  • Non-epithelial histology, including malignant mixed Mullerian tumors
  • Ovarian tumors with low malignant potential (i.e., borderline tumors), low grade serous ovarian cancer or carcinosarcoma
  • History of acute coronary syndromes.
  • History of or current Class II, III, or IV heart failure.
  • History or evidence of known central nervous system (CNS) metastases or carcinomatous meningitis.
  • Significant bleeding disorders, vasculitis or a significant bleeding episode from the Gastrointestinal (GI) tract.
  • History of severe hypersensitivity reactions to antibodies.
  • Systemic steroid therapy.
  • History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
  • Prior organ transplantation including allogenic or autologous stem cell transplantation
  • Prior treatment with anti-cluster of differentiation 47 (CD47) or anti-SIRPα therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05261490


Contacts
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Contact: Pfizer CT.gov Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, California
Sarcoma Oncology Research Center Recruiting
Santa Monica, California, United States, 90403
United States, Florida
Orlando Health Cancer Institute Gynecologic Cancer Center Not yet recruiting
Orlando, Florida, United States, 32806
Orlando Health Cancer Institute Not yet recruiting
Orlando, Florida, United States, 32806
United States, Ohio
Cleveland Clinic taussig Cancer Center Investigational Pharmacy Not yet recruiting
Cleveland, Ohio, United States, 44106
Cleveland Clinic Fairview Hospital Not yet recruiting
Cleveland, Ohio, United States, 44111
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Cleveland Clinic Hillcrest Hospital Not yet recruiting
Mayfield Heights, Ohio, United States, 44124
United States, Oklahoma
Oklahoma Cancer Specialist and Research Institute. LLC Not yet recruiting
Tulsa, Oklahoma, United States, 74146
United States, Pennsylvania
Magee-Womens Hospital of UPMC Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
UPMC Hillman Cancer Center-Investigational Drug Services Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, South Dakota
Avera Cancer Institute Not yet recruiting
Sioux Falls, South Dakota, United States, 57105
United States, Texas
oncology Consultants, P.A. Recruiting
Houston, Texas, United States, 77024
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05261490    
Other Study ID Numbers: TTI-622-02
C4971002 ( Other Identifier: Alias Study Number )
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: January 23, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Epithelial Ovarian Cancer EOC)
Ovarian Cancer
Platinum-Resistant Ovarian Cancer
Cluster of Differentiation 47 (CD47)
TTI-622
Doxorubicin
Immune-oncology
chemotherapy
anti-SIRPα therapy
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action