Phase 2
Completed N=12
Japan PhI/II of GSK2118436 and GSK1120212 Combination in Subjects With BRAF V600E/K Mutation Positive Advanced Solid Tumors (Phase I Part) or Cutaneous Melanoma (Phase II Part)
Source: ClinicalTrials.gov NCT01928940 ↗Enrolled (actual)
12
Serious AEs
8.3%
Results posted
Oct 2015
Primary outcomePrimary: Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) — 6; 1 Participants
Summary
This is a Japanese Phase I/II, open-label, non-controlled study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of the combination of GSK2118436 and GSK1120212 in subjects with BRAF V600E/K mutation positive advanced solid tumors (Phase I part) and BRAF V600E/K mutation positive cutaneous melanoma (Phase II part).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) |
6; 1 | — |
| PRIMARY Phase I: Number of Participants With a Dose-limiting Toxicity (DLT) |
— | — |
| PRIMARY Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) |
1; 1; 1; 2; 1; 3 | — |
| PRIMARY Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters |
1; 1; 1; 1; 3; 1 | — |
| PRIMARY Phase I: Number of Participants With the Indicated Urinalysis Parameters |
6; 0; 2; 1; 6; 0 | — |
| PRIMARY Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status |
1; 4; 1 | — |
| PRIMARY Phase I: Number of Participants With Worst-case On-therapy Increase From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3 |
3; 0; 2; 1 | — |
| PRIMARY Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate |
1; 3; 3 | — |
| PRIMARY Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature |
2; 2; 3 | — |
| PRIMARY Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points |
1.0; 0.8; 0.2; 0.7; 1.4; 1.2 | — |
| PRIMARY Phase I: Change From Baseline in Weight at the Indicated Time Points |
-4.87; -4.43; -4.13; -4.00; -0.62; -0.70 | — |
| PRIMARY Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points |
4; 2; 0; 5; 1; 0 | — |
| PRIMARY Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) |
0; 0; 5; 1; 0; 1 | — |
| PRIMARY Phase II: Number of Participant With Confirmed Overall Response |
5; 5 | <0.0001 sig |
| SECONDARY Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose |
12850.5346; 10075.3530; 11414.9211; 10138.0887; 13485.6357; 10530.0297 | — |
| SECONDARY Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose |
2497.383; 3431.280; 1336.296; 1995.847; 3689.039; 12303.403 | — |
| SECONDARY Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose |
118.36; 84.25; 78.14; 78.29; 105.05; 121.85 | — |
| SECONDARY Phase I: Time of Occurrence of Cmax (Tmax) and Terminal Phase Half Life (t1/2) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose |
4.5398; 2.425; 1.685; 4.2086; 3.410; 1.950 | — |
| SECONDARY Phase I: Number of Participants With Confirmed Overall Response Rate |
5; 3 | <0.0001 sig |
| SECONDARY Phase I: Number of Participants With Unconfirmed Overall Response Rate |
5; 3 | <0.0001 sig |
| SECONDARY Phase I: Progression Free Survival (PFS) |
NA; NA | — |
| SECONDARY Phase I: Duration of Response |
NA; NA | — |
| SECONDARY Phase II: Number of Participants With Unconfirmed Overall Response |
5; 5 | <0.0001 sig |
| SECONDARY Phase II: Progression Free Survival (PFS) |
NA; NA | — |
| SECONDARY Phase II: Duration of Response |
NA; NA | — |
| SECONDARY Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event |
6; 0 | — |
| SECONDARY Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters |
2; 2; 5; 2; 1; 1 | — |
| SECONDARY Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters |
1; 1; 2; 1; 1; 1 | — |
| SECONDARY Phase II: Number of Participants With the Indicated Urinalysis Results |
6; 0; 3; 0; 6; 0 | — |
| SECONDARY Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status |
0; 4; 2 | — |
| SECONDARY Phase II: Number of Participants With Worst-case On-therapy Increase From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3 |
3; 0; 5; 0 | — |
| SECONDARY Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate |
1; 4; 1 | — |
| SECONDARY Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature |
2; 4; 0 | — |
| SECONDARY Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points |
-0.2; 0.3; 0.5; 0.5; -0.2; 0.3 | — |
| SECONDARY Phase II: Change From Baseline in Weight at the Indicated Time Points |
-0.68; -0.22; -0.30; 0.05; -0.32; 0.06 | — |
| SECONDARY Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points |
5; 1; 0; 4; 2; 0 | — |
| SECONDARY Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram |
1; 0; 3; 2; 0; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Capable of given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Male or female age 20 years or greater; able to swallow and retain oral medication.
- BRAF mutation positive advanced solid tumor ( Phase I part). BRAF mutation positive melanoma (Phase II part).
- Measurable disease according to RECIST version 1.1.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Agree to contraception requirements.
- Adequate organ system function.
Exclusion Criteria
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy).
- Phase II part ONLY: Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed.
- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 28 days prior to the study treatment (6 weeks for prior nitrosourea or mitomycin C), or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to the study treatment. Limited radiotherapy within the last 2 weeks. (Note: Ipilimumab treatment must end at least 8 weeks prior to the study treatment.)
- Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to the study treatment.
- Current use of a prohibited medication or requires any of these medications during treatment with the study drugs.
- A history of another malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
- Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures (e.g., uncontrolled diabetes).
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- History of pneumonitis or interstitial lung disease.
- Known HIV infection.
- Certain cardiac abnormality
- A history or current evidence/risk of retinal vein occlusion or central serous retinopathy.
- Pregnant or lactating female.
Data sourced from ClinicalTrials.gov (NCT01928940). 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. Informational only — not medical advice.