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

• ClinicalTrials.gov Identifier: NCT05261490
• Recruitment Status: Recruiting
• First Posted: March 2, 2022
• Last Update Posted: January 23, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

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

Locations

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

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• 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
• 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

• 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:

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