Phase 1
N=86
PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma
Multiple Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT03269136 ↗Enrolled (actual)
86
Serious AEs
65.5%
Results posted
Mar 2025
Primary outcome: Primary: Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03 — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-06863135 monotherapy IV or SC (Drug); PF-06863135 + dexamethasone (Drug); PF-06863135 + lenalidomide (Drug); PF-06863135 + pomalidomide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03 |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Part 2: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria |
60.0 | — |
| PRIMARY Part 2: Duration of Response (DOR) as Per IMWG Criteria |
11.6 | — |
| SECONDARY Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs), Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03 |
2; 3; 2; 3; 2; 5 | — |
| SECONDARY Part 1: Number of Participants With Shifts From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters |
1; 2; 2; 2; 2; 5 | — |
| SECONDARY Part 1: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters |
0; 2; 0; 1; 0; 2 | — |
| SECONDARY Part 1: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Urinalysis |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: ORR as Per IMWG Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: Time to Response (TTR) as Per IMWG Criteria |
22.0; 22.0; 22.0; 42.0; 39.0; 36.0 | — |
| SECONDARY Part 1: Complete Response Rate (CRR) as Per IMWG Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: DOR as Per IMWG Criteria |
25.3; 13.6; NA; NA; 6.7; 17.1 | — |
| SECONDARY Part 1: Duration of Complete Response (DoCR) as Per IMWG Criteria |
25.3; NA; NA; NA; NA; NA | — |
| SECONDARY Part 1: Duration of Stable Disease (DOSD) as Per IMWG Criteria |
1.3; NA; 0.8; NA; 3.4; 3.0 | — |
| SECONDARY Part 1: Progression Free Survival (PFS) as Per IMWG Criteria |
0.4; 0.7; 1.1; 1.7; 1.6; 1.6 | — |
| SECONDARY Part 1: Overall Survival (OS) |
8.2; 8.4; 11.2; 8.1; 16.2; 14.8 | — |
| SECONDARY Part 1: Percentage of Participants With Negative Minimal Residual Disease (MRD) Using IMWG MRD Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: Maximum Observed Concentration (Cmax) of PF-06863135 |
3.639; 4.216; 2.144; 2.277; NA; NA | — |
| SECONDARY Part 1: Area Under the Concentration-Time Profile From Time 0 to End of Dosing Interval (AUCtau) |
16.82; 16.93; 9.643; 10.91; NA; NA | — |
| SECONDARY Part 1C and Part 1D: Plasma Concentration of Lenalidomide and Pomalidomide |
NA; NA; 70.70; 13.60; 70.60; 32.70 | — |
| SECONDARY Part 1: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06863135 |
0; 0; 0; 1; 0; 2 | — |
| SECONDARY Part 1: Concentration of Soluble Cytokines in Serum |
2.10; 2.10; 2.10; 2.10; 2.10; 2.10 | — |
| SECONDARY Part 2: Number of Participants With AEs, Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03 |
15; 12; 13; 11; 3 | — |
| SECONDARY Part 2: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters |
15 | — |
| SECONDARY Part 2: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters |
8 | — |
| SECONDARY Part 2: Number of Participants With Shifts From Grade <=2 to Grade 3 or 4 Post-Baseline in Urinalysis |
— | — |
| SECONDARY Part 2: CRR as Per IMWG Criteria |
33.3 | — |
| SECONDARY Part 2: DoCR as Per IMWG Criteria |
9.4 | — |
| SECONDARY Part 2: TTR as Per IMWG Criteria |
40.0 | — |
| SECONDARY Part 2: DOSD as Per IMWG Criteria |
11.6 | — |
| SECONDARY Part 2: PFS as Per IMWG Criteria |
10.4 | — |
| SECONDARY Part 2: OS |
12.1 | — |
| SECONDARY Part 2: Percentage of Participants With Negative MRD After Treatment With PF-06863135 Using IMWG MRD Criteria |
33.33; 13.33 | — |
| SECONDARY Part 2: Number of Participants With ADA and NAb Against PF-06863135 |
0; 0 | — |
| SECONDARY Part 2: Concentration of Soluble Cytokines in Serum |
2.10; 2.10; 2.10; 2.10; 2.10; 2.10 | — |
Summary
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.
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
Data sourced from ClinicalTrials.gov (NCT03269136). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.