Breast Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Solid Tumor, Adult
Conditions
Keywords
cancer, solid tumor, PROCLAIM, CX-2009, PROBODY™ Therapeutic, Drug Conjugate, Antibody drug conjugate, CD166
Brief summary
The purpose of this first-in-human study of CX-2009 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-2009 in adult subjects with metastatic or locally advanced unresectable solid tumors. PROCLAIM: PRObody CLinical Assessment In Man CX-2009 clinical trial 001 PROBODY is a trademark of CytomX Therapeutics, Inc
Interventions
DRUGCX-2009
CX-2009 Monotherapy
Sponsors
CytomX Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed diagnosis of metastatic or locally advanced unresectable tumors 2. Patients demonstrating disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, 3. Agreement to provide mandatory archival tissue or fresh biopsy. 4. At least 18 years of age.
Exclusion criteria
1. Active or chronic corneal disorder, history of corneal transplantation, active herpetic keratitis, and active ocular conditions requiring ongoing treatment/monitoring 2. Serious concurrent illness, including clinically relevant active infection 3. History of or current active autoimmune diseases 4. Significant cardiac disease such as recent myocardial infarction 5. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease; 6. Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm; 7. History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy; 8. Currently receiving anticoagulation therapy with warfarin; 9. Major surgery (requiring general anesthesia) within 3 months prior to dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | 21 days for the Q3W schedule, 28 days for the Q2W schedule | All AEs will be captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 and considered for assessment of DLTs as outlined by the criteria in Protocol Table 5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | Median total on-study follow-up of 18.4 weeks. | Efficacy will be assessed via objective response rate (ORR) by RECIST version 1.1. ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) on two consecutive tumor assessments with scan dates at least 4 weeks apart according to RECIST (version 1.1, refer to SAP section 13.1.1). Complete criteria for RECIST 1.1 are provided as an appendix to the protocol. \> \> For as long as a subject continues follow-up for response in the study, CT/MRI/Tumor assessment are to be conducted every 8 (+/- 1) weeks from the first dose of CX 2009 with assessment for response per \> RECIST Version 1.1 |
Countries
Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The study was conducted in 4 parts (Part A, Part A2, Part B, and Part C1). Doses used were as follows: Parts A, A2, and B dosed 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 9, and 10 mg/kg every 21 days, and Part C1: 4 and 6 mg/kg dosed every 14 days. A2 biomarker cohorts and Cohort B are pooled with A cohorts receiving the identical dose and schedule. Study periods are reported as defined in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| A 0.25 mg/kg Q3W Part A 0.25 mg/kg Q3W | 1 |
| A 0.5 mg/kg Q3W Part A 0.5 mg/kg Q3W | 3 |
| A 1 mg/kg Q3W Part A 1 mg/kg Q3W | 3 |
| A 2 mg/kg Q3W Part A 2 mg/kg Q3W | 3 |
| A, A2 4 mg/kg Q3W Parts A & A2 4 mg/kg Q3W | 10 |
| A, A2 5 mg/kg Q3W Parts A & A2 5 mg/kg Q3W | 9 |
| A, A2 6 mg/kg Q3W Parts A & A2 6 mg/kg Q3W | 9 |
| A, A2 7 mg/kg Q3W Parts A & A2 7 mg/kg Q3W | 12 |
| A, A2 8 mg/kg Q3W Parts A & A2 8 mg/kg Q3W | 22 |
| A, A2 9 mg/kg Q3W Parts A & A2 9 mg/kg Q3W | 9 |
| A, A2 10 mg/kg Q3W Parts A & A2 10 mg/kg Q3W | 8 |
| C1 4 mg/kg Q2W Part C1 4 mg/kg Q2W | 4 |
| C1 6 mg/kg Q2W Part C1 6 mg/kg Q2W | 6 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Discontinuation--Follow-Up Period | Death | 1 | 3 | 3 | 1 | 4 | 3 | 5 | 3 | 9 | 5 | 5 | 1 | 1 |
| Study Discontinuation--Follow-Up Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Study Discontinuation--Follow-Up Period | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Study Discontinuation--Follow-Up Period | Termination by Sponsor | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 5 | 0 | 0 | 3 | 2 |
| Study Discontinuation--Follow-Up Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 4 | 1 | 1 | 3 | 0 | 1 |
| Study Discontinuation--Treatment Period | Death | 0 | 0 | 0 | 1 | 2 | 1 | 1 | 2 | 4 | 1 | 0 | 0 | 1 |
| Study Discontinuation--Treatment Period | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Study Discontinuation--Treatment Period | Termination by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Study Discontinuation--Treatment Period | Withdrawal by Subject | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | A 0.25 mg/kg Q3W | A 0.5 mg/kg Q3W | A 1 mg/kg Q3W | A 2 mg/kg Q3W | A, A2 4 mg/kg Q3W | A, A2 5 mg/kg Q3W | A, A2 6 mg/kg Q3W | A, A2 7 mg/kg Q3W | A, A2 8 mg/kg Q3W | A, A2 9 mg/kg Q3W | A, A2 10 mg/kg Q3W | C1 4 mg/kg Q2W | C1 6 mg/kg Q2W | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54 years | 60 years | 59 years | 68 years | 68 years | 49 years | 62 years | 59 years | 56.5 years | 56 years | 54 years | 59.5 years | 53.5 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 10 Participants | 7 Participants | 8 Participants | 9 Participants | 20 Participants | 7 Participants | 7 Participants | 4 Participants | 6 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 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) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants | 8 Participants | 8 Participants | 6 Participants | 17 Participants | 7 Participants | 7 Participants | 4 Participants | 6 Participants | 81 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants | 7 Participants | 6 Participants | 12 Participants | 18 Participants | 7 Participants | 7 Participants | 4 Participants | 4 Participants | 78 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 21 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 3 / 3 | 3 / 3 | 2 / 3 | 6 / 10 | 4 / 9 | 6 / 9 | 6 / 12 | 13 / 22 | 7 / 9 | 6 / 8 | 1 / 4 | 2 / 6 |
| other Total, other adverse events | 1 / 1 | 3 / 3 | 2 / 3 | 3 / 3 | 10 / 10 | 9 / 9 | 9 / 9 | 12 / 12 | 22 / 22 | 9 / 9 | 8 / 8 | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 | 0 / 3 | 1 / 3 | 2 / 10 | 2 / 9 | 3 / 9 | 5 / 12 | 10 / 22 | 5 / 9 | 3 / 8 | 1 / 4 | 1 / 6 |
Outcome results
Primary
The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy
All AEs will be captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 and considered for assessment of DLTs as outlined by the criteria in Protocol Table 5.
Time frame: 21 days for the Q3W schedule, 28 days for the Q2W schedule
Population: A DLT-evaluable subject is defined as one having received at least 1 dose of CX-2009 (or CX 2009 and CX-072) and then having completed the full DLT observation period (either 21 or 28 days depending on the schedule), or one who subsequently withdrew due to a drug-related toxicity.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A 0.25 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 1 Participants |
| A 0.25 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A 0.5 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 3 Participants |
| A 0.5 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A 1 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A 1 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 3 Participants |
| A 2 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 3 Participants |
| A 2 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2 4 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 10 Participants |
| A, A2 4 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2 5 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2 5 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 9 Participants |
| A, A2 6 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 9 Participants |
| A, A2 6 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2, B 7 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2, B 7 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 12 Participants |
| A, A2 8 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 1 Participants |
| A, A2 8 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 21 Participants |
| A, A2 9 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| A, A2 9 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 9 Participants |
| A, A2 10 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 8 Participants |
| A, A2 10 mg/kg Q3W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| C1 4 mg/kg Q2W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 4 Participants |
| C1 4 mg/kg Q2W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 0 Participants |
| C1 6 mg/kg Q2W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants experiencing DLT | 2 Participants |
| C1 6 mg/kg Q2W | The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy | Participants not experiencing DLTs | 4 Participants |
Secondary
Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy
Efficacy will be assessed via objective response rate (ORR) by RECIST version 1.1. ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) on two consecutive tumor assessments with scan dates at least 4 weeks apart according to RECIST (version 1.1, refer to SAP section 13.1.1). Complete criteria for RECIST 1.1 are provided as an appendix to the protocol. \> \> For as long as a subject continues follow-up for response in the study, CT/MRI/Tumor assessment are to be conducted every 8 (+/- 1) weeks from the first dose of CX 2009 with assessment for response per \> RECIST Version 1.1
Time frame: Median total on-study follow-up of 18.4 weeks.
Population: The response evaluable population includes all subjects in the safety analysis population who have an adequate baseline disease assessment and at least one post-baseline disease assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A 0.25 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A 0.5 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A 1 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A 2 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 4 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 5 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 6 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2, B 7 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 8 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 9 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| A, A2 10 mg/kg Q3W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 1 Participants |
| C1 4 mg/kg Q2W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 0 Participants |
| C1 6 mg/kg Q2W | Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy | 1 Participants |