PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors

Study Overview
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Brief Summary
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The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.

Official Title
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A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: PF-06804103
* Drug: PF-06804103 + Palbociclib +Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only) HER2 positive and negative breast cancer (Part 2A) HER2 negative breast cancer (Part 1B & Part 2B) Performance status of 0 or 1 Adequate bone marrow, kidney and liver function Exclusion Criteria: Known CNS disease including, but not limited to, metastases History of exposure to certain cumulative doses of anthracyclines Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy Active and clinically significant bacterial, fungal, or viral infection Abnormal cardiac function defined by a LVEF <50% by ECHO or MUGA Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06804103<br>Study Treatment | Drug: PF-06804103<br>* Dose Escalation Part - 1A Dose Expansion Part - 2A<br>|
| Experimental: PF-06804103+Combination Regimen<br>Study Treatment | Drug: PF-06804103 + Palbociclib +Letrozole<br>* Dose Escalation - Part 1B Dose Expansion - Part 2B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-Limiting Toxicities (DLTs) | First cycle DLTs in order to determine the maximum tolerated dose of monotherapy. | Part 1A: Baseline through Day 21; Part 1B: Baseline through Day 28 | 
| Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Assessment of all available safety data in order to determine the safety and tolerability of monotherapy and combination therapy | Part 1 and Part 2: Baseline through LSLV (up to approximately 2 years) | 
| Number of participant with objective response | To investigate preliminary antitumor activity | Part 2: Baseline through LSLV (up to approximately 2 years) | 
| Duration of Response (DR) | To investigate preliminary antitumor activity | Part 2: Baseline through LSLV (up to approximately 2 years) | 
| Progression-Free Survival (PFS) | To investigate preliminary antitumor activity | Part 2: Baseline through LSLV (up to approximately 2 years) | 
| Time to Tumor Progression (TTP) | To investigate preliminary antitumor activity | Part 2: Baseline through LSLV (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) - Part 1A | To understand single and multiple dose parameters | Cycle 1 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycle 2 Day 1 0 and 1 hour, Cycle 3 Day 1 0 and 1 hour, Cycle 4 Day 1 0, 1, 4 and 24 hour, Day 4, Day 8, Day 15, and Day 1 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Maximum Observed Concentration (Cmax) - Part 2A | To understand single and multiple dose parameters | Cycles 1 & 4 on Day 1 at 0, 1, 4 hours, and on Day 15; Cycles 2 & 3 on Day 1 at 0 & 1 hour; Every subsequent cycle pn Day 1 at 0 and 1 hour (cycle is 21 days) up to 24 months | 
| Maximum Observed Concentration (Cmax) Part B | To understand single and multiple dose parameters | Cycles 1 & 4 on Day 1 at 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15 at 0 & 1 hour; Cycles 2 & 3 on Day 1 at 0 & 1 hour, Cycles 2 & 3 on Day 15 at 0 & 1 hour; Every subsequent cycle on Day 1 at 0 & 1 hour (cycle is 28 days) up to 24 months | 
| Time to reach maximum observed concentration (Tmax) - Part 1A | To understand single and multiple dose parameters | Cycles 1 & 4 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycles 2 & 3 Day 1: 0 and 1 hour, and Day 1: 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Time to reach maximum observed concentration (Tmax) - Part 2A | To understand single and multiple dose parameters | Cycles 1 & 4 on Day 1 at 0, 1, 4 hours, and on Day 15; Cycles 2 & 3 on Day 1 at 0 & 1 hour; Every subsequent cycle pn Day 1 at 0 and 1 hour (cycle is 21 days) up to 24 months | 
| Time to reach maximum observed concentration (Tmax) - Part B | To understand single and multiple dose parameters | Cycles 1 & 4 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycles 2 & 3 Day 1: 0 and 1 hour, and Day 1: 0 and 1 hour of subsequent cycles (cycle is 28 days) up to 24 months | 
| Area under the curve from time zero to end of dosing interval (AUCtau) Part 1A | To understand single and multiple dose parameters | Cycle 1 Day 1 0, 1 4, and 24 hours, Day 4, Day 8 and Day 15, Cycle 2 Day 1 0 and 1 hour, Cycle 3 Day 1 0 and 1 hour, Cycle 4 Day 1 0, 1, 4 and 24 hour, Day 4, Day 8, Day 15, and Day 1 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Area under the curve from time zero to end of dosing interval (AUCtau) Part 2A | To understand single and multiple dose parameters | Cycles 1 and 4: Day 1: 0, 1, 4 hours, and Day 15; Cycle 2 and 3, Day 1: 0 and 1 hour, and Day 1 at 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Area under the curve from time zero to end of dosing interval (AUCtau) Part B | To understand single and multiple dose parameters | Cycles 1 and 4: Day 1: 0, 1, 4 hours, Day 2, Day 4, Day 8 and Day 15 at 0 and 1 hour; Cycle 2 and 3, Day 1: 0 and 1 hour and Day 15 at 0 and 1 hour, and Day 1 at 0 and 1 hour of subsequent cycles (cycle is 28 days) up to 24 months | 
| Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 1A | To understand single and multiple dose parameters | Cycle 1 & Cycle 4 Day 1: 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 2A | To understand single and multiple dose parameters | Cycle 1 & Cycle 4 Day 1: 0, 1, 4 hours, & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 21 days) up to 24 months | 
| Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part B | To understand single and multiple dose parameters | Cycle 1 & Cycle 4 Day 1: 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 28 days) up to 24 months | 
| Incidence and titers of anti-drug antibodies Part A | To evaluate the immunogenicity of the drug | Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsequent cycle (each cycle is 21 days) up to 24 months | 
| Incidence and titers of anti-drug antibodies Part B | To evaluate the immunogenicity of the drug | Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 28 days) up to 24 months | 
| Incidence and titers of neutralizing antibodies Part A | To evaluate the immunogenicity of the drug | Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 21 days) up to 24 months | 
| Incidence and titers of neutralizing antibodies Part B | To evaluate the immunogenicity of the drug | Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 28 days) up to 24 months | 
| Number of participant with objective response | Document antitumor activity | Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months | 
| Progression-Free Survival (PFS) | Document antitumor activity | Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months | 
| HER2 expression level in patients with documented anti-tumor activity | Explore preliminary antitumor activity | Baseline and Cycle 3 Day 1 (for monotherapy: each cycle is 21 days; for combination therapy: each cycle is 28 days) | 
| Duration of Response (DR) | Document antitumor activity | Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months | 
| Time to Tumor Progression (TTP) | Document antitumor activity | Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2, PF-06804103, ADC, breast cancer, neoplasms, solid tumors, human epidermal growth receptor 2