Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Neoplasms, Immunoconjugate, Tumor microenvironment alkalinization
Brief summary
The primary purpose of this research study is to evaluate how safe, how well tolerated and how effective a range of doses of L-DOS47 in combination with standard doublet therapy of pemetrexed/carboplatin in patients with Stage IV (TNM M1a and M1b) recurrent or metastatic non-squamous Non-Small Cell Lung Cancer.
Detailed description
It is planned that patients will receive 4 cycles of combination treatment with L-DOS47 + pemetrexed/carboplatin. Patients who have not progressed following the 4 cycles of combination treatment and who have not experienced unacceptable toxicity will have the opportunity to continue to receive L-DOS47 treatment for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression. Patients who are unable to complete 4 cycles of L-DOS47 + pemetrexed/carboplatin combination treatment due to pemetrexed/carboplatin toxicity will have the opportunity to continue receiving L-DOS47 treatment following discontinuation of pemetrexed/carboplatin, for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression.
Interventions
DRUGL-DOS47
A treatment cycle will be 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle.
Sponsors
Theradex
Helix BioPharma Corporation
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, dose escalation where patients are recruited into cohorts of escalating doses of L-DOS47 (0.59 up to 12.0 µg/kg) in combination with pemetrexed and carboplatin.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Male or female patient ≥ 18 years of age 2. Histologically or cytologically confirmed non-squamous NSCLC 3. EGFR-mutation positive patients must have progressed on or had intolerance to an EGFR small molecule tyrosine kinase inhibitor 4. Patients whose tumors harbor an anaplastic lymphoma kinase (ALK) translocation must have progressed on or had intolerance to an ALK inhibitor; 5. No prior adjuvant chemotherapy within 1 year of the first treatment day if there is recurrent disease 6. At least 1 site of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and minimum life expectancy of ≥ 3 months 8. Adequate bone marrow, renal and liver function Main
Exclusion criteria
1. Histologic evidence of predominantly squamous cell NSCLC 2. Brain metastasis and/or leptomeningeal disease (known or suspected) 3. Peripheral neuropathy \> CTCAE grade 1 4. Possibility of a curative local treatment (surgery and/or radiotherapy) 5. Previous chemotherapy except adjuvant treatment with progression of disease documented ≥ 12 months after end of adjuvant treatment 6. Having received treatment in another clinical study within the 30 days prior to commencing study treatment or having side effects of a prior study drug that are not recovered to grade ≤ 1 or baseline, except for alopecia 7. Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Up to 12 weeks | Beginning with the start of study treatment at Cycle 1 Day 1 up to the last study visit: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. Beginning with the AE reporting period at the start of study treatment at Cycle 1 Day 1 up to the last study visit; |
| Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | Up to 21 days | A DLT was defined as the occurrence of any of the following events (according to NCI CTCAE version 4.0) that are considered to be (possibly/probably/definitely) related to L-DOS47 and occurring within 21 days after commencing study treatment: * Haematological adverse events ≥ grade 4 * Non-haematological adverse events ≥ grade 3 * One instance each of any two unique grade 2 adverse events |
| Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 21 days | Defined as the highest dose level at which ≤ 1 of 6 patients experiences a dose limiting toxicity (DLT) as assessed during the first treatment cycle. If no DLT are reported, it is assumed that the maximum tolerated dose of L-DOS47 in combination with pemetrexed/carboplatin was not reached. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Up to 12 weeks | Objective tumor response will be assessed according to RECIST version 1.1 in patients who have completed at least 2 cycles of study treatment and who have at least 1 post-treatment disease assessment; where complete response (CR) is the disappearance of all target lesions and partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Percentage of Patients Receiving a Sustained Clinical Benefit | Up to 12 weeks | Defined as the percentage of patients who have achieved complete response, partial response, or stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin; where complete response (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and stable disease (SD) is where neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD, at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study). |
Countries
United States
Participant flow
Recruitment details
Study subjects were enrolled at three study sites in the United States from April 2014 to August 2019.
Pre-assignment details
A total of 14 study subjects diagnosed with metastatic or recurrent non-small cell lung cancer (NSCLC) were enrolled to receive planned escalating doses of L-DOS47 (0.59 - 12.0 ug/kg) in combination with standard doses of carboplatin and pemetrexed.
Participants by arm
| Arm | Count |
|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 0.59 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 3 |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 0.78 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 6 |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 1.5 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 1 |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 3.0 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 1 |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 0.78 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 1 |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 9.0 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 2 |
| L-DOS47 12.0 ug/kg in Combination With Pemetrexed and Carboplatin Subjects were to receive a weekly dose 12.0 µg/kg of L-DOS47 by IV infusion in combination with standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], where a treatment cycle was 21 days, with patients receiving L-DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle for a total of four treatment cycles. Subjects had the option to continue on weekly doses of L-DOS47 for long as there was clinical benefit and well-tolerated. | 0 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | L-DOS47 12.0 ug/kg in Combination With Pemetrexed and Carboplatin | Total | L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 0 Participants |
| Age, Continuous | 62.8 years STANDARD_DEVIATION 5.27 | 48 years STANDARD_DEVIATION 0 | 56 years STANDARD_DEVIATION 0 | 67 years STANDARD_DEVIATION 0 | 65.5 years STANDARD_DEVIATION 10.61 | — | 63.5 years STANDARD_DEVIATION 7.42 | 70.0 years STANDARD_DEVIATION 3 |
| ECOG Performance Status ECOG=0 | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 4 Participants | 1 Participants |
| ECOG Performance Status ECOG=1 | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | — | 10 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | — | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | — | 11 Participants | 3 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | — | 7 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | — | 7 Participants | 2 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 2 / 6 | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 2 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 1 / 1 | 1 / 1 | 1 / 1 | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 3 / 6 | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 2 | 0 / 0 |
Outcome results
Primary
Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin
Defined as the highest dose level at which ≤ 1 of 6 patients experiences a dose limiting toxicity (DLT) as assessed during the first treatment cycle. If no DLT are reported, it is assumed that the maximum tolerated dose of L-DOS47 in combination with pemetrexed/carboplatin was not reached.
Time frame: 21 days
Population: Any subject who experienced a dose-limiting toxicity (DLT); a DLT is also assumed to have occurred if a patient does not receive all scheduled doses of L-DOS47 due to toxicity
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin | 0 Participants |
Primary
Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin.
A DLT was defined as the occurrence of any of the following events (according to NCI CTCAE version 4.0) that are considered to be (possibly/probably/definitely) related to L-DOS47 and occurring within 21 days after commencing study treatment: * Haematological adverse events ≥ grade 4 * Non-haematological adverse events ≥ grade 3 * One instance each of any two unique grade 2 adverse events
Time frame: Up to 21 days
Population: Any subject who has received all scheduled doses of L-DOS47 in Cycle 1; a DLT is assumed to have occurred if a patient does not receive all scheduled doses of L-DOS47 due to toxicity
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. | 0 Participants |
Primary
Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin
Beginning with the start of study treatment at Cycle 1 Day 1 up to the last study visit: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. Beginning with the AE reporting period at the start of study treatment at Cycle 1 Day 1 up to the last study visit;
Time frame: Up to 12 weeks
Population: Any subject who has received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 2 Participants |
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 3 Participants |
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 0 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 3 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 6 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 5 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 1 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 0 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 1 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 1 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 1 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 1 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs related to L-DOS47 | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent AEs | 2 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs related to L-DOS47 | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin | Treatment emergent SAEs | 1 Participants |
Secondary
Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1
Objective tumor response will be assessed according to RECIST version 1.1 in patients who have completed at least 2 cycles of study treatment and who have at least 1 post-treatment disease assessment; where complete response (CR) is the disappearance of all target lesions and partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 12 weeks
Population: Efficacy-evaluable population includes those patients who have completed at least two cycles of study treatment and had at least one post-baseline tumor assessment. For patients with fewer than two cycles of study treatment, there had to be clear evidence of clinical progression. For patients to be evaluable for stable disease, the duration of stable disease must be at least 42 days from the first dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 0 Participants |
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 1 Participants |
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 0 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 3 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 1 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 2 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 1 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 0 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 0 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 1 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 0 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 1 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Partial response | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Progressive disease | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 | Stable disease | 2 Participants |
Secondary
Percentage of Patients Receiving a Sustained Clinical Benefit
Defined as the percentage of patients who have achieved complete response, partial response, or stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin; where complete response (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and stable disease (SD) is where neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD, at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study).
Time frame: Up to 12 weeks
Population: Efficacy-evaluable population includes those patients who have completed at least two cycles of study treatment and had at least one post-baseline tumor assessment. For patients with fewer than two cycles of study treatment, there had to be clear evidence of clinical progression. For patients to be evaluable for stable disease, the duration of stable disease must be at least 42 days from the first dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 1 Participants |
| L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 4 Participants |
| L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 1 Participants |
| L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 1 Participants |
| L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 0 Participants |
| L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin | Percentage of Patients Receiving a Sustained Clinical Benefit | 2 Participants |