Trial Outcomes & Findings for Erlotinib Hydrochloride and Onalespib Lactate in Treating Patients With Recurrent or Metastatic EGFR-Mutant Non-small Cell Lung Cancer (NCT NCT02535338)

Last Updated: 2025-03-03

Results Overview

Adverse events were graded by CTCAE, v4. DLTs deﬁned as ≥Gr 3 non-hematologic toxicity except nausea, vomiting, or diarrhea that could be controlled by appropriate medical intervention or prophylaxis and that resolved within 48 hours, except electrolyte toxicities that can be corrected within 48 hours. Gr 3 rash attributed to the combination was considered a DLT if it remained Gr 3 despite maximal medical management for \> 72 hours. Hematologic toxicities qualifying as DLTs included febrile neutropenia; Gr 4 neutropenia for \> 7 days or thrombocytopenia \< 25,000/mm3 (Gr 4) if associated with a bleeding event that did not result in hemodynamic instability but required an elective platelet transfusion; or a life-threatening bleeding event that resulted in urgent intervention and admission to an intensive care unit. Delay in starting cycle 2 of ≥14 days due to toxicity related to one or more protocol drugs was also considered a DLT. The ﬁrst 28-day cycle was considered the DLT period.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

28 days from the start of treatment.

Results posted on

2025-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Overall Study STARTED	3	8
Overall Study COMPLETED	3	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Erlotinib Hydrochloride and Onalespib Lactate in Treating Patients With Recurrent or Metastatic EGFR-Mutant Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Total n=11 Participants Total of all reporting groups
Age, Continuous	51 years n=5 Participants	62.5 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days from the start of treatment.

Population: Two DLTs (Gr 3 maculopapular rash and Gr 3 hypophosphatemia) occurred at dose level 1.

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Number of Participants With at Least One Dose Limiting Toxicity (DLT)	2 participants	0 participants

PRIMARY outcome

Timeframe: 28 days from start of treatment.

The maximum tolerated dose (MTD) of Onalespib IV in combination with 150 mg Erlotinib PO daily is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=11 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Recommended Phase II Dose	120 mg/m2	—

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: This outcome measure has been addressed in primary outcome measures 1 \& 2.

During the first course of therapy patients will be monitored for dose-limiting toxicities (DLT). Dose escalation will follow a 3+3 design, motivated by the desire to limit the incidence of dose-limiting toxicity to the lowest feasible levels and determine the recommended phase II dose. This outcome measure has been addressed in primary outcome measures 1 \& 2.

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Number of Participants With Dose Limiting Toxicities.	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to at least 1 year

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Number of Subject With Overall Response	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death from any cause, whichever occurs first, assessed up to at least 1 year

Population: The majority of patients (10/11) had lung cancers harboring EGFR ex20ins and were heavily pretreated.

Progression-free survival will be summarized as time from first protocol treatment until progression or death from any cause, using the product-limit Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Progression-free Survival	NA Months Interval 0.9 to NA - The Median and upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	4.5 Months Interval 1.4 to NA - The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Up to at least 1 year

Outcome measures

Outcome measures
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=8 Participants Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Number of Subject With Overall Response (Recommended Phase II Dose)	0 Participants	—

Adverse Events

Dose Level 1 - Onalespib IV 150 mg/m2

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Dose Level -1 - Onalespib IV 120 mg/m2

Serious events: 3 serious events

Other events: 8 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 - Onalespib IV 150 mg/m2 n=3 participants at risk Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies	Dose Level -1 - Onalespib IV 120 mg/m2 n=8 participants at risk Patients receive 150 mg erlotinib hydrochloride PO daily and onalespib lactate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Onalespib Lactate: Given IV Pharmacological Study: Correlative studies
Gastrointestinal disorders Colitis	33.3% 1/3 • Number of events 2 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/8 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 2/8 • Number of events 2 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastric hemorrhage	33.3% 1/3 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/8 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 1/3 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/8 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive Disease	0.00% 0/3 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	12.5% 1/8 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Expression aphasia	0.00% 0/3 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	12.5% 1/8 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Confusion	33.3% 1/3 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/8 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress	0.00% 0/3 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	12.5% 1/8 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/8 • Adverse events occurred over a period of 2 years and 4 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 626-218-5265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60