Hematologic Malignancies, Solid Tumor
Conditions
Keywords
PF-07901800, ABCL, Aggressive B-cell lymphoma, CLL, Chronic lymphocytic leukemia, CTCL, Cutaneous T-Cell Lymphoma, HL, Hodgkin lymphoma, IBCL, Indolent B-cell lymphoma, MDS, Myelodysplastic syndromes, MPN, Myeloproliferative neoplasms, MM, Multiple Myeloma, PTCL, Peripheral T-cell lymphomas, SCLC, Small Cell Lung Cancer, T-cell lymphoma, Rituximab, Nivolumab, TTI-621, Solid Tumor, Hematologic Malignancies, Lymphoma, CD47, SIRPα-IgG1 Fc
Brief summary
Multicenter, open-label, phase 1a/1b trial of PF-07901800 (TTI-621) in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.
Detailed description
This is a trial of PF-07901800 (TTI-621) in subjects with relapsed or refractory hematologic malignancies and selected solid tumors. TTI-621 (SIRPαFc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory do not eat (anti phagocytic) signal to macrophages. This trial will be conducted in 2 phases and 4 parts: Phase 1a Part 1 (escalation phase) and Phase 1b Parts 2-4 (expansion phase). In the dose Escalation Phase (phase 1a Part 1), subjects with lymphoma will be enrolled in sequential dose cohorts to receive TTI-621 to characterize safety, tolerability, pharmacokinetics, and the maximum-tolerated dose (MTD). In the Expansion Phase (phase 1b Parts 2-4), TTI-621 will be given to subjects with a variety of hematologic malignancies and selected solid tumors to further define safety and to characterize efficacy. In the Expansion Phase Part 2, the safety and efficacy of TTI-621 will also be assessed when it is given in combination with other anti-cancer drugs. The dose of TTI-621 to be delivered in the Expansion Phase Parts 2-3 of the study may be increased or decreased based on the subject's tolerability and on the subject's response to treatment. In the phase 1b dose optimization of the study (Part 4), further dose escalation of TTI-621, beyond the dose determined during phase 1a dose escalation, will be pursued in patients with relapsed and/or refractory CTCL following a 3+3 escalation design and using a revised DLT criteria to further evaluate the safety and tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b Parts 2-3. Secondary objectives include further characterization of the pharmacokinetics, pharmacodynamics, and development of ADA; and to gain preliminary evidence of the anti-tumor activity of TTI-621 in subjects with a variety of hematologic malignancies and selected solid tumors. In addition, the safety of TTI-621 will be evaluated in combination with other anti-cancer agents. Pfizer decided terminating this study for administrative reasons on 22Mar2022 (stopping enrollment as of 15Apr2022). The decision wasn't due to safety concerns or requests from regulatory authorities.
Interventions
DRUGPF-0791800 (TTI-621)
Monotherapy
DRUGPF-07901800 (TTI-621) plus Rituximab
Combination therapy
DRUGPF-07901800 (TTI-621) plus Nivolumab
Combination therapy
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Intervention model description
Phase 1a/1b trial of PF-07901800 (TTI-621) for relapsed or refractory hematologic malignancies and selected solid tumors were conducted in 4 parts. In the dose escalation phase (Part 1), advanced lymphomas were enrolled in sequential dose cohorts for safety, tolerability, PK, and MTD. In the expansion phase (Part 2), subjects with various hematologic malignancies and selected solid tumors were treated at recommended dose determined in phase 1a (Part 1) for safety and efficacy. In the expansion phase (Part 3), 2 cohorts (cutaneous T-cell lymphoma and peripheral T-cell lymphoma) were evaluated for potentially further studied using Simon 2-stage design. In the phase 1b dose optimization (Part 4), further dose escalation was investigated in patients with relapsed and/or refractory CTCL following a 3+3 escalation and revised DLT criteria.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
MAJOR ELIGIBILITY CRITERIA: Phase 1a Escalation • Histologically documented, measurable, advanced lymphomas, transfusion-independence Phase 1b Expansion (Part 2 and 3) • Advanced malignancy: IBCL, ABCL, cHL, AML, ALL, MDS, MPN, SCLC, PTCL and CTCL; measurable disease who have relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1 prior systemic attempt for PTCL). For CTCL, extracorporeal photochemotherapy (ECP) considered a systemic therapy. Local radiation and topical agents are not systemic therapies. Phase 1b dose optimization (Part 4) • Histologically confirmed diagnosis of CTCL (both Mycosis Fungoides and Sezary Syndrome): Failed at least 2 prior systemic therapies for CTCL (Systemic therapy does not include local radiation therapy or topical agents); History of histologically documented diagnosis of CTCL stage IB to IVB Inclusion Criteria (all subjects): * Advanced measurable malignancy with previously progressed on, or currently progressing on standard anticancer therapy or for whom no other approved conventional therapy exists * Eastern Cooperative Oncology Group (ECOG) 0-2 * Adequate hematologic, hepatic, renal, and coagulation function; fresh or archived tumor tissue available for immunohistochemistry * Recovery from prior treatments and/or surgeries; no history of hemolytic anemia or bleeding diathesis. * AML M3 (French American British, FAB, classification) (i.e., acute promyelocytic leukemia \[APL\]) excluded
Exclusion criteria
* Known current central nervous system disease involvement or untreated brain metastases * Allogeneic transplant within 30 days prior to the planned start of treatment or subjects with active graft-vs-host disease with the exception of Grade 1 skin involvement * History of hemolytic anemia or bleeding diathesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Part 1: Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 1 was 414 days) | An adverse event (AE) was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Part 1: Day 1 of dosing up to Pre-dose on Day 22 | DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration ( Absolute Neutrophil Count (ANC) less than (\<) 1.0 \* 10\^9/L. fever greater than (\>) 38.5° Degree Celsius (C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage. |
| Part 2 and 3: Number of Participants With TEAEs and TESAEs | Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 2 was 1793 days and for Part 3 was 938 days) | An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. |
| Part 4: Number of Participants With TEAEs and TESAEs | Part 4: Day 1 of dosing up to 1 year of safety follow-up visit after the last dose (maximum treatment exposure for Part 4 was 667 days) | An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE event was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. |
| Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | Part 4: Day 1 of dosing up to Pre-dose on Day 22 | DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration (ANC \< 1.0 x 109/L, fever \> 38.5°C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 and 3 Combined: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | Part 2 and 3: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | Results for this outcome measure was reported for Part 2 and Part 3 combined. |
| Part 2 and 3 Combined: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | Part 2 and 3: Week 1 end of infusion (EOI) | CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumour cells. Results are reported for combined Part 2 and 3. |
| Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | Part 2 and 3: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 2 was 1793 days and for Part 3 was 938 days) | A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> 4-fold dilution increase in titer from baseline in \> 1 post-treatment sample (treatment-boosted). |
| Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete remission and partial remission. Lugano classification (Cheson et al., 2014) and refinement (Cheson et al., 2016) were used for tumor response assessment for lymphomas by computed tomography (CT)-based criteria and complete metabolic response (CMR) or partial metabolic response (PMR) by positron emission tomography (PET-CT) based criteria were used for evaluation. Lymphomas evaluated by Lugano Classification include aggressive B-cell lymphoma (ABCL), Hodgkin's lymphoma (HL), Non-Hodgkin's lymphoma, indolent B-cell lymphoma (IBCL), peripheral T-cell lymphoma (PTCL), and part of T-cell lymphoma (TCL). |
| Parts 2 and 3: Overall Response Rate (ORR)-Olsen 2011-Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete response and partial response. Clinical endpoints and response criteria (Olsen et al., 2011) for in CTCL (mycosis fungoides and Sezary syndrome) and TCL were used for assessment. Tumor types evaluated included Cutaneous T-cell lymphoma (CTCL) and a part of T-cell lymphoma (TCL). |
| Part 2: Overall Response Rate (ORR)-Savona 2015- Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete remission, partial remission and marrow response. International Consortium Proposal of Uniform Response Criteria for Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) in adults (Savona et al., 2015) was used for assessment of tumors. Tumor types evaluated include Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN). |
| Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | Part 4: Week 1 end of infusion (EOI) | CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumor cells. |
| Part 2: Overall Response Rate (ORR)- Hallek 2008- Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete response or complete remission, complete response or complete remission with incomplete marrow recovery, partial response. International Workshop on CLL update of the NCI 1996 Guidelines (Hallek et al., 2008) was used for assessment of tumors. Tumor types evaluated include chronic lymphocytic leukemia (CLL). |
| Part 2: Overall Response Rate (ORR)- Durie 2006- Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete response, stringent complete response, very good partial response, partial response. International Uniform Response Criteria for Multiple Myeloma (Durie et al., 2006). was used for assessment of tumors.Tumor types evaluated include Multiple Myeloma (MM). |
| Part 1: Maximum Plasma Concentration (Cmax) of TTI-621 | Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | — |
| Part 2: Overall Response Rate (ORR)- Bohnsack 2014- Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had irComplete Response, IrPartial Response. Immune-Related Response Criteria: RECIST (Bohnsack et al., 2014) was used for assessment of tumor. Tumor types evaluated included Small Cell Lung Cancer (SCLC). |
| Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | DoR was defined, in participants who achieved a response as time from the first date of response to the first date of recurrent or progression disease. Participants without recurrent or progression disease were censored on date of the last adequate disease assessment, date of initiation of anticancer treatment or death of death, whichever was the earliest. |
| Parts 2 and 3: Progression Free Survival (PFS) | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | PFS was defined as the number of weeks from the date of the first dose of study drug to the earliest of documented recurrent or progressive disease or death due to any cause without prior progression. The progression or censoring date was determined based on described conventions (Food and Drug Administration, 2007). Kaplan-Meier method was used. |
| Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | Part 4: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | — |
| Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | Part 4: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | — |
| Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | Part 4: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 4 was 667 days) | A participant was ADA (or NAb) positive if: (1) baseline titer is missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> \[4-fold dilution increase\] in titer from baseline in \> 1 post-treatment sample (treatment-boosted). |
| Part 4: Overall Response Rate (ORR) | From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had complete response, partial response. Lymphomas evaluated include Non-Hodgkin's Lymphoma. Clinical endpoints and response criteria in mycosis fungoides and Sezary syndrome (Olsen et al., 2011). |
| Part 4: Duration of Response (DoR) | From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months) | DoR was defined, in participants who achieved a response as time from the first date of response to the first date of recurrent or progression disease. Participants without recurrent or progression disease were censored on date of the last adequate disease assessment, date of initiation of anticancer treatment or death of death, whichever was the earliest. |
| Part 4: Overall Response Rate (ORR) in Cutaneous T-Cell Lymphoma (CTCL) Both Fungoides and Sezary Syndrome | From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. |
| Part 2: Overall Response Rate (ORR)- Cheson 2003- Disease Indication | From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months) | ORR is presented in this outcome measure as number of responders. Responders were those who had morphologic leukemia-free state, morphologic complete remission, morphologic complete remission with incomplete blood count recovery, partial remission. International Working Group for trials in AML (Cheson et al., 2003) was used for assessment of tumor. Tumor types evaluated include Acute Myeloid Leukemia (AML). |
| Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | — |
| Part 1: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | Part 1: Week 1 end of infusion (EOI) | CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumour cells . |
| Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | Part 1: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 1 was 414 days) | A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> \[4-fold dilution increase\] in titer from baseline in \>1 post-treatment sample (treatment-boosted). |
| Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621 | Part 2 and 3: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1 | Results for this outcome measure was reported for Part 2 and Part 3 combined. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 249 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg Participants with advanced relapsed or refractory lymphomas received TTI-621 0.05 milligram per kilogram (mg/kg) infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 3 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg Participants with advanced relapsed or refractory lymphomas received TTI-621 0.1 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 3 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg Participants with advanced relapsed or refractory lymphomas received TTI-621 0.2 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 7 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg Participants with advanced relapsed or refractory lymphomas received TTI-621 0.3 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 5 |
| Part 2: Ontorpacept (PF-07901800/TTI-621) Monotherapy Participants with a broader variety of hematologic malignancies and selected solid tumors, received a 0.2 mg/kg/week TTI-621 infusion until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 107 |
| Part 2: Ontorpacept (PF-07901800/TTI-621)+ Nivolumab Combination Participants with cHL received 0.1 mg/kg/week TTI-621 infusion along with 3 mg/kg nivolumab given every 2 weeks or a fixed dose per current FDA approved package insert for cHL.If required dose of TTI-621 could be increased up to 0.5 mg/kg/week. Participants received TTI-621 monotherapy upon completion of combination partner regimen/unacceptable toxicity to the combination regimen. | 11 |
| Part 2: Ontorpacept (PF-07901800/TTI-621) + Rituximab Combination Participants with CD20-positive malignancies received 0.1 mg/kg/week TTI-621 infusion along with 375 mg/m\^2 rituximab given weekly (1 cycle) for up to 8 cycles according to the institutional standard of care. Participants received TTI-621 monotherapy upon completion of combination partner regimen/unacceptable toxicity to the combination regimen. | 40 |
| Part 3: Ontorpacept (PF-07901800/TTI-621) Monotherapy Participants with CTCL and PTCL, received a 0.2 mg/kg/week TTI-621 infusion. Initial 2 weeks of 0.2 mg/kg treatment followed by intraparticipant dose intensification at an increment of 0.1 mg/kg per week up to 0.5 mg/kg within 5-8 weeks until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 42 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) 0.5 mg/kg Participants with relapsed or refractory CTCL received TTI-621 0.5 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 3 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) 0.7 mg/kg Participants with relapsed or refractory CTCL received TTI-621 0.7 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 3 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) 1.0 mg/kg Participants with relapsed or refractory CTCL received TTI-621 1.0 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 6 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) 1.4 mg/kg Participants with relapsed or refractory CTCL received TTI-621 1.4 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 3 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) 2.0 mg/kg Participants with relapsed or refractory CTCL received TTI-621 2.0 mg/kg infusion once weekly until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 12 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg Participants with relapsed or refractory CTCL received a 2.0 mg/kg TTI-621 infusion once every 2 weeks until disease progression, unacceptable toxicity, or other reasons for treatment discontinuation occurred. | 4 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Phase 1a Escalation | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Phase 1a Escalation | Informed Consent Withdrawn | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Phase 1a Escalation | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Phase 1a Escalation | Other | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Phase 1a Escalation | Progressive Disease | 2 | 3 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Death | 0 | 0 | 0 | 0 | 50 | 0 | 25 | 16 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Informed Consent Withdrawn | 0 | 0 | 0 | 0 | 16 | 1 | 3 | 8 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Lost to Follow-up | 0 | 0 | 0 | 0 | 4 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Other | 0 | 0 | 0 | 0 | 6 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Progressive Disease | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 and 3: Phase 1b Expansion | Study Terminated By Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 4: Phase 1b Dose Optimization | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 5 | 1 |
| Part 4: Phase 1b Dose Optimization | Informed Consent Withdrawn | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 1 | 1 |
| Part 4: Phase 1b Dose Optimization | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 4: Phase 1b Dose Optimization | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
| Part 4: Phase 1b Dose Optimization | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 4: Phase 1b Dose Optimization | Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2: Ontorpacept (PF-07901800/TTI-621) Monotherapy | Part 2: Ontorpacept (PF-07901800/TTI-621)+ Nivolumab Combination | Part 2: Ontorpacept (PF-07901800/TTI-621) + Rituximab Combination | Part 3: Ontorpacept (PF-07901800/TTI-621) Monotherapy | Part 4: Ontorpacept (PF-07901800/TTI-621) 0.5 mg/kg | Part 4: Ontorpacept (PF-07901800/TTI-621) 0.7 mg/kg | Part 4: Ontorpacept (PF-07901800/TTI-621) 1.0 mg/kg | Part 4: Ontorpacept (PF-07901800/TTI-621) 1.4 mg/kg | Part 4: Ontorpacept (PF-07901800/TTI-621) 2.0 mg/kg | Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 65 - < 75 Years | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 36 Participants | 0 Participants | 17 Participants | 11 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 74 Participants |
| Age, Customized < 65 Years | 2 Participants | 3 Participants | 6 Participants | 2 Participants | 52 Participants | 11 Participants | 19 Participants | 20 Participants | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 7 Participants | 1 Participants | 130 Participants |
| Age, Customized 75 - < 85 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 19 Participants | 0 Participants | 4 Participants | 10 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 43 Participants |
| Age, Customized >= 85 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 8 Participants | 2 Participants | 4 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 94 Participants | 9 Participants | 34 Participants | 32 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 11 Participants | 3 Participants | 209 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 2 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 12 Participants | 1 Participants | 1 Participants | 7 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 15 Participants |
| Race (NIH/OMB) White | 3 Participants | 0 Participants | 5 Participants | 5 Participants | 85 Participants | 10 Participants | 31 Participants | 30 Participants | 2 Participants | 1 Participants | 5 Participants | 3 Participants | 9 Participants | 2 Participants | 191 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 46 Participants | 5 Participants | 10 Participants | 18 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 96 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 61 Participants | 6 Participants | 30 Participants | 24 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 10 Participants | 3 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 1 / 7 | 1 / 5 | 52 / 107 | 0 / 11 | 27 / 40 | 16 / 42 | 0 / 3 | 0 / 3 | 2 / 6 | 0 / 3 | 5 / 12 | 1 / 4 |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 7 / 7 | 5 / 5 | 100 / 107 | 11 / 11 | 34 / 40 | 36 / 42 | 3 / 3 | 2 / 3 | 6 / 6 | 3 / 3 | 12 / 12 | 4 / 4 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 7 | 2 / 5 | 43 / 107 | 2 / 11 | 13 / 40 | 15 / 42 | 1 / 3 | 1 / 3 | 2 / 6 | 0 / 3 | 3 / 12 | 3 / 4 |
Outcome results
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration ( Absolute Neutrophil Count (ANC) less than (\<) 1.0 \* 10\^9/L. fever greater than (\>) 38.5° Degree Celsius (C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage.
Time frame: Part 1: Day 1 of dosing up to Pre-dose on Day 22
Population: The DLT-evaluable set included participants who had received all 3 doses within the DLT evaluation period, or participants who experienced an AE, meeting DLT criteria during that time. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.
Time frame: Part 1: Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 1 was 414 days)
Population: Safety population included all the participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 7 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
Primary
Part 2 and 3: Number of Participants With TEAEs and TESAEs
An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.
Time frame: Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 2 was 1793 days and for Part 3 was 938 days)
Population: Analysis population included all the participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TEAEs | 103 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TESAEs | 43 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TESAEs | 15 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TEAEs | 40 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TEAEs | 11 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TESAEs | 2 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TEAEs | 37 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3: Number of Participants With TEAEs and TESAEs | TESAEs | 13 Participants |
Primary
Part 4: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration (ANC \< 1.0 x 109/L, fever \> 38.5°C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage.
Time frame: Part 4: Day 1 of dosing up to Pre-dose on Day 22
Population: The DLT-evaluable set included participants who had received all 3 doses within the DLT evaluation period, OR participants who experienced an AE, meeting DLT criteria during that time. As 2.0mg/kg Q2W cohort was not a part of escalation for dose optimization, and not relevant to DLT assessment hence this outcome measure was not analyzed for Q2W arm. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Part 4: Number of Participants With TEAEs and TESAEs
An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE event was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.
Time frame: Part 4: Day 1 of dosing up to 1 year of safety follow-up visit after the last dose (maximum treatment exposure for Part 4 was 667 days)
Population: Analysis population included all the participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 3 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 3 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 6 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 2 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 3 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 12 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 3 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TEAEs | 4 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Number of Participants With TEAEs and TESAEs | TESAEs | 3 Participants |
Secondary
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621
Time frame: Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: PK evaluable set included treated participants with adequate blood sampling to estimate at least one pharmacokinetic PK parameter. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 1200.722 Nanogram*hour/milliliter | — |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 6178.488 Nanogram*hour/milliliter | Standard Deviation 844.463 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 18873.939 Nanogram*hour/milliliter | Standard Deviation 6213.503 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 36782.700 Nanogram*hour/milliliter | Standard Deviation 8700.626 |
Secondary
Part 1: Maximum Plasma Concentration (Cmax) of TTI-621
Time frame: Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: Pharmacokinetic (PK)-evaluable set included treated participants with adequate blood sampling to estimate at least one pharmacokinetic PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Maximum Plasma Concentration (Cmax) of TTI-621 | 136.594 Nanogram per milliliter | Standard Deviation 64.248 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Maximum Plasma Concentration (Cmax) of TTI-621 | 366.636 Nanogram per milliliter | Standard Deviation 67.433 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Maximum Plasma Concentration (Cmax) of TTI-621 | 823.137 Nanogram per milliliter | Standard Deviation 153.681 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Maximum Plasma Concentration (Cmax) of TTI-621 | 1579.799 Nanogram per milliliter | Standard Deviation 518.546 |
Secondary
Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb)
A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> \[4-fold dilution increase\] in titer from baseline in \>1 post-treatment sample (treatment-boosted).
Time frame: Part 1: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 1 was 414 days)
Population: Immunogenicity analysis population included all treated participants with at least one ADA sample (pre-dose or post-treatment) analyzed. Here, Number of Participants Analyzed signifies number of participants who were ADA or NAb evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
Secondary
Part 1: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells
CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumour cells .
Time frame: Part 1: Week 1 end of infusion (EOI)
Population: This outcome measure was not analyzed since CD47 data for Part 1 was not collected as the assay was not set up when enrolling the Part 1 participants. Hence, no participants evaluable for this outcome measure.
Secondary
Part 2 and 3 Combined: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621
Results for this outcome measure was reported for Part 2 and Part 3 combined.
Time frame: Part 2 and 3: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: PK -evaluable set included treated participants with adequate blood sampling to estimate at least one PK parameter. Here, Number of participants analyzed signifies number of evaluable participants for this outcome measure. Data for only those arms \[according to dose\] are reported for this outcome measure which had any evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3 Combined: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 9330 Nanogram*hour per milliliter | Standard Deviation 10300 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3 Combined: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 20000 Nanogram*hour per milliliter | Standard Deviation 10400 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3 Combined: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 16100 Nanogram*hour per milliliter | — |
Secondary
Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621
Results for this outcome measure was reported for Part 2 and Part 3 combined.
Time frame: Part 2 and 3: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: PK evaluable set included treated participants with adequate blood sampling to estimate at least one PK parameter. Here, Number of participants analyzed signifies number of evaluable participants for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621 | 341 Nanogram per milliliter | Standard Deviation 160 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621 | 1020 Nanogram per milliliter | Standard Deviation 1270 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621 | 673 Nanogram per milliliter | — |
Secondary
Part 2 and 3 Combined: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells
CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumour cells. Results are reported for combined Part 2 and 3.
Time frame: Part 2 and 3: Week 1 end of infusion (EOI)
Population: Safety population included all the participants who received at least one dose of study treatment. Here, Number of participants analyzed signifies number of evaluable participants for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3 Combined: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 24.99 Percentage of Cells | Standard Deviation 16.54 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3 Combined: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 31.39 Percentage of Cells | Standard Deviation 17.28 |
Secondary
Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb)
A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> 4-fold dilution increase in titer from baseline in \> 1 post-treatment sample (treatment-boosted).
Time frame: Part 2 and 3: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 2 was 1793 days and for Part 3 was 938 days)
Population: Immunogenicity analysis population included all treated participants with at least one ADA sample (pre-dose or post-treatment) analyzed. Here, Number of Participants Analyzed signifies number of participants who were ADA or NAb evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 14 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 5 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
Secondary
Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations
ORR is presented in this outcome measure as number of responders. Responders were those who had complete remission and partial remission. Lugano classification (Cheson et al., 2014) and refinement (Cheson et al., 2016) were used for tumor response assessment for lymphomas by computed tomography (CT)-based criteria and complete metabolic response (CMR) or partial metabolic response (PMR) by positron emission tomography (PET-CT) based criteria were used for evaluation. Lymphomas evaluated by Lugano Classification include aggressive B-cell lymphoma (ABCL), Hodgkin's lymphoma (HL), Non-Hodgkin's lymphoma, indolent B-cell lymphoma (IBCL), peripheral T-cell lymphoma (PTCL), and part of T-cell lymphoma (TCL).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 4 Participants |
| Part 4: TTI-621 2 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 9 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 3 Participants |
| Parts 2 and 3: T-cell Lymphoma (TCL) | Part 2 and 3: Overall Response Rate (ORR) - Lugano Classification (Cheson 2014) and Refinement (Cheson 2016) Disease Indications and Nivolumab/Rituximab Combinations | 3 Participants |
Secondary
Part 2: Overall Response Rate (ORR)- Bohnsack 2014- Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had irComplete Response, IrPartial Response. Immune-Related Response Criteria: RECIST (Bohnsack et al., 2014) was used for assessment of tumor. Tumor types evaluated included Small Cell Lung Cancer (SCLC).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2: Overall Response Rate (ORR)- Bohnsack 2014- Disease Indication | 0 Participants |
Secondary
Part 2: Overall Response Rate (ORR)- Cheson 2003- Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had morphologic leukemia-free state, morphologic complete remission, morphologic complete remission with incomplete blood count recovery, partial remission. International Working Group for trials in AML (Cheson et al., 2003) was used for assessment of tumor. Tumor types evaluated include Acute Myeloid Leukemia (AML).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2: Overall Response Rate (ORR)- Cheson 2003- Disease Indication | 2 Participants |
Secondary
Part 2: Overall Response Rate (ORR)- Durie 2006- Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had complete response, stringent complete response, very good partial response, partial response. International Uniform Response Criteria for Multiple Myeloma (Durie et al., 2006). was used for assessment of tumors.Tumor types evaluated include Multiple Myeloma (MM).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2: Overall Response Rate (ORR)- Durie 2006- Disease Indication | 0 Participants |
Secondary
Part 2: Overall Response Rate (ORR)- Hallek 2008- Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had complete response or complete remission, complete response or complete remission with incomplete marrow recovery, partial response. International Workshop on CLL update of the NCI 1996 Guidelines (Hallek et al., 2008) was used for assessment of tumors. Tumor types evaluated include chronic lymphocytic leukemia (CLL).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2: Overall Response Rate (ORR)- Hallek 2008- Disease Indication | 0 Participants |
Secondary
Part 2: Overall Response Rate (ORR)-Savona 2015- Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had complete remission, partial remission and marrow response. International Consortium Proposal of Uniform Response Criteria for Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) in adults (Savona et al., 2015) was used for assessment of tumors. Tumor types evaluated include Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 2: Overall Response Rate (ORR)-Savona 2015- Disease Indication | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 2: Overall Response Rate (ORR)-Savona 2015- Disease Indication | 1 Participants |
Secondary
Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621
Time frame: Part 4: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: PK -evaluable set included treated participants with adequate blood sampling to estimate at least one PK parameter. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 88800 Nanogram*hour per milliliter | Standard Deviation 12300 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 116000 Nanogram*hour per milliliter | Standard Deviation 38800 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 212000 Nanogram*hour per milliliter | Standard Deviation 85700 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 383000 Nanogram*hour per milliliter | Standard Deviation 49600 |
| Part 4: TTI-621 2 mg/kg | Part 4: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621 | 638000 Nanogram*hour per milliliter | Standard Deviation 120000 |
Secondary
Part 4: Duration of Response (DoR)
DoR was defined, in participants who achieved a response as time from the first date of response to the first date of recurrent or progression disease. Participants without recurrent or progression disease were censored on date of the last adequate disease assessment, date of initiation of anticancer treatment or death of death, whichever was the earliest.
Time frame: From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months)
Population: Analysis population included all the participants who received at least one dose of study treatment. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Duration of Response (DoR) | NA Months |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Duration of Response (DoR) | NA Months |
| Part 4: TTI-621 2 mg/kg | Part 4: Duration of Response (DoR) | NA Months |
Secondary
Part 4: Maximum Plasma Concentration (Cmax) of TTI-621
Time frame: Part 4: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1
Population: The Pharmacokinetic (PK)-evaluable Set consists of treated participants with adequate blood sampling to estimate at least one pharmacokinetic PK parameter. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 4040 Nanogram per milliliter | Standard Deviation 110 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 6190 Nanogram per milliliter | Standard Deviation 1100 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 10000 Nanogram per milliliter | Standard Deviation 4400 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 15400 Nanogram per milliliter | Standard Deviation 2470 |
| Part 4: TTI-621 2 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 23600 Nanogram per milliliter | Standard Deviation 4530 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Maximum Plasma Concentration (Cmax) of TTI-621 | 18800 Nanogram per milliliter | — |
Secondary
Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb)
A participant was ADA (or NAb) positive if: (1) baseline titer is missing or negative and participants had \>1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \> \[4-fold dilution increase\] in titer from baseline in \> 1 post-treatment sample (treatment-boosted).
Time frame: Part 4: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 4 was 667 days)
Population: Immunogenicity analysis population includes all treated participants with at least one (ADA) Anti-Drug Antibody sample (pre-dose or post-treatment) analyzed. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | ADA Positive: Overall Incidence | 0 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) | NAb Positive: Overall Incidence | 0 Participants |
Secondary
Part 4: Overall Response Rate (ORR)
ORR is presented in this outcome measure as number of responders. Responders were those who had complete response, partial response. Lymphomas evaluated include Non-Hodgkin's Lymphoma. Clinical endpoints and response criteria in mycosis fungoides and Sezary syndrome (Olsen et al., 2011).
Time frame: From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months)
Population: Analysis population included all the participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Overall Response Rate (ORR) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Overall Response Rate (ORR) | 0 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Overall Response Rate (ORR) | 1 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Overall Response Rate (ORR) | 1 Participants |
| Part 4: TTI-621 2 mg/kg | Part 4: Overall Response Rate (ORR) | 2 Participants |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Overall Response Rate (ORR) | 0 Participants |
Secondary
Part 4: Overall Response Rate (ORR) in Cutaneous T-Cell Lymphoma (CTCL) Both Fungoides and Sezary Syndrome
ORR is presented in this outcome measure as number of responders.
Time frame: From first dose of study till the progressive disease/death or withdrawal (maximum observation 6 years 10 months)
Population: Data for this outcome measure is not available as analysis was not performed because: 1) due to futility and heterogenicity of respective data of the parameters of organ system (i.e., skin, blood, lymph node, and viscera; 2) the Olsen 2011 criteria already defined the Global Response Score to determine the Global Response (GR) consisting of the 4 components which (GR) was more important assessment affecting overall prognosis.
Secondary
Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells
CD47 is a cell-surface protein expressed on multiple normal cell types and often at high levels on many malignant tumor cells.
Time frame: Part 4: Week 1 end of infusion (EOI)
Population: Safety population included all the participants who received at least one dose of study treatment. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 62.25 Percentage of cells | Standard Deviation 12.65 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 65.49 Percentage of cells | Standard Deviation 24.8 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 37.17 Percentage of cells | Standard Deviation 32.93 |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 57.09 Percentage of cells | Standard Deviation 23.72 |
| Part 4: TTI-621 2 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 65.00 Percentage of cells | Standard Deviation 5.97 |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Part 4: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells | 49.51 Percentage of cells | Standard Deviation 10.83 |
Secondary
Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations
DoR was defined, in participants who achieved a response as time from the first date of response to the first date of recurrent or progression disease. Participants without recurrent or progression disease were censored on date of the last adequate disease assessment, date of initiation of anticancer treatment or death of death, whichever was the earliest.
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | NA Months |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | NA Months |
| Part 2: Myeloproliferative Neoplasms (MPN) | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 8.3 Months |
| Part 2: Ontorpacept (PF-07901800/TTI-621)+ Nivolumab Combination | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 9.2 Months |
| Part 3: Peripheral T-cell Lymphoma (PTCL) | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 12.0 Months |
| Part 2: Ontorpacept (PF-07901800/TTI-621) + Rituximab Combination | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 3.1 Months |
| Parts 2 and 3: Cutaneous T-cell Lymphoma (CTCL) | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 1.9 Months |
| Parts 2 and 3: T-cell Lymphoma (TCL) | Parts 2 and 3: Duration of Response (DoR)- Disease Indication and Nivolumab/Rituximab Combinations | 8.3 Months |
Secondary
Parts 2 and 3: Overall Response Rate (ORR)-Olsen 2011-Disease Indication
ORR is presented in this outcome measure as number of responders. Responders were those who had complete response and partial response. Clinical endpoints and response criteria (Olsen et al., 2011) for in CTCL (mycosis fungoides and Sezary syndrome) and TCL were used for assessment. Tumor types evaluated included Cutaneous T-cell lymphoma (CTCL) and a part of T-cell lymphoma (TCL).
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Parts 2 and 3: Overall Response Rate (ORR)-Olsen 2011-Disease Indication | 2 Participants |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Parts 2 and 3: Overall Response Rate (ORR)-Olsen 2011-Disease Indication | 5 Participants |
Secondary
Parts 2 and 3: Progression Free Survival (PFS)
PFS was defined as the number of weeks from the date of the first dose of study drug to the earliest of documented recurrent or progressive disease or death due to any cause without prior progression. The progression or censoring date was determined based on described conventions (Food and Drug Administration, 2007). Kaplan-Meier method was used.
Time frame: From first dose of study till the progressive disease/ death or withdrawal (maximum observation 6 years 10 months)
Population: Full analysis set included all participants who received at least 1 dose of study treatment. Number of Participants Analyzed refers to participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.05 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 1.6 Months |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.1 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 0.8 Months |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.2 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 1.4 Months |
| Part 1: Ontorpacept (PF-07901800/TTI-621) 0.3 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 3.1 Months |
| Part 4: TTI-621 2 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 1.4 Months |
| Part 4: Ontorpacept (PF-07901800/TTI-621) Q2W / 2.0 mg/kg | Parts 2 and 3: Progression Free Survival (PFS) | 0.8 Months |
| Parts 2 and 3: T-cell Lymphoma (TCL) | Parts 2 and 3: Progression Free Survival (PFS) | 1.1 Months |
| Part 2: Myeloproliferative Neoplasms (MPN) | Parts 2 and 3: Progression Free Survival (PFS) | 11.0 Months |
| Part 2: Ontorpacept (PF-07901800/TTI-621)+ Nivolumab Combination | Parts 2 and 3: Progression Free Survival (PFS) | 3.5 Months |
| Part 3: Peripheral T-cell Lymphoma (PTCL) | Parts 2 and 3: Progression Free Survival (PFS) | 1.7 Months |
| Part 2: Ontorpacept (PF-07901800/TTI-621) + Rituximab Combination | Parts 2 and 3: Progression Free Survival (PFS) | 1.7 Months |
| Parts 2 and 3: Cutaneous T-cell Lymphoma (CTCL) | Parts 2 and 3: Progression Free Survival (PFS) | 5.4 Months |
| Parts 2 and 3: T-cell Lymphoma (TCL) | Parts 2 and 3: Progression Free Survival (PFS) | 2.6 Months |