Description:
To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients
with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose
and select the recommended Phase 2 dose.
Title
- Brief Title: PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma
- Official Title: A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF PF-06863135, A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH IMMUNOMODULATORY AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)
Clinical Trial IDs
- ORG STUDY ID:
C1071001
- SECONDARY ID:
2019-000822-24
- NCT ID:
NCT03269136
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| PF-06863135 monotherapy IV or SC | BCMA-CD3 bispecific antibody | PF-06863135 |
| PF-06863135 + dexamethasone | BCMA-CD3 bispecific antibody + dexamethasone | PF-06863135 + dexamethasone |
| PF-06863135 + lenalidomide | BCMA-CD3 bispecific antibody + lenalidomide | PF-06863135 + lenalidomide |
| PF-06863135 + pomalidomide | BCMA-CD3 bispecific antibody + pomalidomide | PF-06863135 + pomalidomide |
Purpose
To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients
with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose
and select the recommended Phase 2 dose.
Detailed Description
Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety,
pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced
multiple myeloma who have relapsed from or are refractory to standard therapy. This is a two
part study; Part 1 will assess the safety and tolerability of increasing dose levels of
PF-06863135 and Part 2 will evaluate safety and anti-myeloma activity of PF-06863135 at the
RP2Ds determined in Part 1.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| PF-06863135 | Experimental | BCMA-CD3 bispecific antibody | - PF-06863135 monotherapy IV or SC
|
| PF-06863135 + dexamethasone | Experimental | BCMA-CD3 bispecific antibody + dexamethasone | - PF-06863135 + dexamethasone
|
| PF-06863135 + lenalidomide | Experimental | BCMA-CD3 bispecific antibody + lenalidomide | - PF-06863135 + lenalidomide
|
| PF-06863135 + pomalidomide | Experimental | BCMA-CD3 bispecific antibody + pomalidomide | - PF-06863135 + pomalidomide
|
Eligibility Criteria
Inclusion Criteria:
- Relapsed/refractory multiple myeloma
- Progressed or are intolerant of established therapies including proteasome inhibitor,
immunomodulatory drug, and anti-CD38 antibody
- Performance Status of 0- 1 ( Performance Score 2 is permitted only if due to
underlying myeloma)
- Adequate bone marrow, hematological, kidney and liver function
- Resolved acute effects of any prior therapy to baseline severity
- Not pregnant
Exclusion Criteria:
- Recent history of other malignancies
- History of active autoimmune disorders
- Any form of primary immunodeficiency
- Active and clinically significant bacterial, fungal, or viral infection
- Evidence of active mucosal or internal bleeding
- History of severe immune-mediated adverse event with prior immunomodulatory treatment
- Major surgery within 4 weeks of study treatment start
- Radiation therapy within 2 weeks of study treatment start
- History of stem cell transplant (autologous or allogeneic) within 100 days prior to
study enrollment
- Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry
- Less than 30 days since last dose of antibody based therapies or less than 5
half-lives since last dose of previous therapy
- Requirement for systemic immune suppressive medication except as permitted in the
protocol
- Current requirement for chronic blood product support
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) |
| Time Frame: | At the end of Cycle 1 (each Cycle is 21 or 28 days) |
| Safety Issue: | |
| Description: | Number of participants with DLTs |
Secondary Outcome Measures
| Measure: | To evaluate incidence of treatment emergent adverse events and laboratory abnormalities |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities |
| Measure: | To evaluate anti-myeloma activity by objective response rate (ORR) in dose escalation |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma |
| Measure: | To evaluate anti-myeloma activity by time to event endpoints |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Time from start date to date of first documentation of event (response or progression by IMWG criteria or death) |
| Measure: | To evaluate anti-myeloma activity by duration of event endpoints |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Time from first assessment of event endpoint (response or stable disease) to last assessment of (response or stable disease) by IMWG criteria |
| Measure: | Impact of treatment on systemic soluble immune factors |
| Time Frame: | 9 months on treatment |
| Safety Issue: | |
| Description: | Pre and post dose quantification of soluble cytokines in serum. |
| Measure: | Maximum plasma concentration (Cmax) of PF-06863135 |
| Time Frame: | Cycle 1 Day 1 and Cycle 2 Day 1 (3 to 4 weeks) |
| Safety Issue: | |
| Description: | Peak concentration of PF-06863135 during first cycle |
| Measure: | Trough serum concentrations of PF-06863135 and dexamethasone |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Trough serum concentrations of PF-06863135 and dexamethasone at selected cycles |
| Measure: | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-06863135 |
| Time Frame: | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | AUC of PF-06863135 will be calculated at selected cycles |
| Measure: | Incidence and titers of anti-drug antibodies and neutralizing antibodies against PF-06863135 |
| Time Frame: | From baseline and scheduled timepoints post dose through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) |
| Safety Issue: | |
| Description: | Number of participants with the presence of anti-PF-06863135 antibodies |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Pfizer |
Trial Keywords
- Multiple Myeloma
- relapse/ refractory multiple myeloma
- bispecific antibody
- bispecific
- BCMA
- BCMA- CD3 bispecific
- Phase 1
- PF-06863135
- dexamethasone
- lenalidomide
- pomalidomide
Last Updated
July 2, 2021
