Solid Tumors
Conditions
Brief summary
Prospective, open-label, dose-ranging, uncontrolled phase I study with escalating doses of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors. The study objectives are: To determine the MTD and the RD of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors. To characterize the safety profile and feasibility of this combination in this study population. To characterize the pharmacokinetics of this combination and to detect major drug-drug PK interactions. To obtain preliminary information on the clinical antitumor activity of this combination.
Interventions
DRUGGemcitabine plus PM060184
Sponsors
PharmaMar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily signed and dated written informed consent prior to any specific study procedure. 2. Age ≥ 18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 (see APPENDIX 1). 4. Life expectancy ≥ 3 months. 5. Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists: * Breast cancer non-candidate for hormone therapy alone. * Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas). * Locally advanced or metastatic head and neck cancer. * Non-small cell lung cancer (NSCLC). * Germ cell tumors (GCTs). * Biliary tract adenocarcinoma. * Adenocarcinoma or carcinoma of unknown primary site (UKPS). * Cervix carcinoma. * Gastrointestinal stromal tumor (GIST). * Urothelial cancer. 6. Expansion cohort at the RD: All patients must have: * Measurable disease according to RECIST v.1.1 (or Choi criteria and/or EORTC metabolic response criteria for solid tumors, in the case of GIST); or * Evaluable disease by serum markers in the case of ovarian cancer \[Gynecologic Cancer Intergroup (GCIG) specific criteria\]; and * Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria. 7. Wash-out periods: at least three weeks since the last anticancer therapy, including radiation therapy (RT) in more than 35% of the bone marrow; at least three weeks since the last biological/investigational therapy \[excluding monoclonal antibodies (MAbs)\]; at least four weeks since the last MAb-containing therapy; and at least six weeks since nitrosoureas and mitomycin C (systemic). In the case of hormonesensitive breast cancer progressing while on hormone therapy, the latter must be either stopped up to one week before or continued without changes during the trial. 8. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study): * Platelet count ≥ 100 x 109/l, hemoglobin ≥ 9.0 g/dl and ANC ≥ 1.0 x 109/l. * AST and ALT ≤ 3.0 x ULN, independently of the presence of liver metastases. * AP ≤ 2.5 x ULN (≤ 5 x ULN if disease-related). * Total bilirubin ≤ 1.5 x ULN. * International Normalized Ratio (INR) \< 1.5 (except if patient is on oral anticoagulation therapy). * Calculated creatinine clearance (CrCl) ≥ 50 ml/minute (using Cockcroft and Gault's formula; see APPENDIX 2). * Albumin ≥ 2.5 g/dl. 9. Recovery to grade ≤ 1 from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or asthenia). 10. Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiplegated acquisition (MUGA) within normal range (according to institutional standards). 11. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and/or double barrier.
Exclusion criteria
1. Concomitant diseases/conditions: * History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year. * Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment. * Known chronic active hepatitis or cirrhosis * Active uncontrolled infection \[i.e., antibiotic, antifungal or antiviral intervention indicated or surgical procedure (i.e., pleural or deep abscess drainage) conducted within 15 days prior to inclusion\]. * Known human immunodeficiency virus (HIV) infection. * Current or prior history of grade ≥ 2 peripheral sensory and/or motor neuropathy. * Prior treatment with oxaliplatin. * Limitation of the patient's ability to comply with the treatment or follow-up protocol. * Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study. 2. Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement. 3. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding. 4. Patients who have had RT in more than 35% of the bone marrow. 5. Treatment with any investigational product within 30 days before the first infusion. 6. Prior treatment with PM060184. 7. Prior treatment with gemcitabine-containing therapy for advanced disease (adjuvant therapy is allowed, provided not more than six cycles were administered and relapse occurred more than six months after the last drug administration), and/or: * Patients who have previously discontinued gemcitabine-containing regimens due to gemcitabine-related toxicity. 8. Known hypersensitivity to gemcitabine or any component of the formulation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | From the start of treatment to the end of cycle one which are 3 weeks | Dose-limiting toxicities were defined as: * Grade 4 neutropenia lasting \>3 days * Grade≥3 febrile neutropenia of any duration or neutropenic sepsis * Grade 4 thrombocytopenia or grade 3 with any major bleeding episode requiring a platelet transfusion * Grade 4 ALT/AST increase, or grade 3 lasting \>7 days * Treatment-related grade≥2 ALT/AST increase concomitantly with ≥2 x ULN total bilirubin increase and normal AP * Any other grade≥3 non-hematological AE that was suspected to be related to study drugs, except nausea/vomiting, hypersensitivity reactions, extravasations, grade 3 asthenia lasting less than one week, anorexia, and non-clinically relevant isolated biochemical abnormalities * Delay in the administration of Cycle 2 of the combination exceeding seven (+1) days of the treatment due date due to any AEs related to study drugs. * The following circumstances were to be discussed between the Principal Investigator and the Sponsor, and the final consensus had to be documented |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Benefit | Every two cycles (every six weeks ± one week) until Cycle 4, and then every three cycles (every nine weeks ± one week) while on treatment, up to 2 years | Clinical benefit defined as any response or stable disease ≥4 months. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
Countries
Spain, United States
Participant flow
Recruitment details
A total of 57 patients were enrolled at three investigational sites, and 55 patients were treated with the GEM/PM060184 combination. Two patients were never treated. Patients participated in this trial between 12 December 2014 and 11 July 2019 (last follow-up). The first dose of the first cycle was given on 10 February 2015 and the last dose of the last cycle was given on 7 June 2019.
Participants by arm
| Arm | Count |
|---|---|
| GEM/PM060184 Dose Level I Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level I: 800 mg/m\^2 GEM / 6.0 mg/m\^2 PM060184 | 5 |
| GEM/PM060184 Dose Level II Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level II: 800 mg/m\^2 GEM / 7.0 mg/m\^2 PM060184 | 7 |
| GEM/PM060184 Dose Level III Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level III: 1000 mg/m\^2 GEM / 6.0 mg/m\^2 PM060184 | 4 |
| GEM/PM060184 Dose Level IV Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level IV: 1000 mg/m\^2 GEM / 8.0 mg/m\^2 PM060184 | 5 |
| GEM/PM060184 Dose Level V Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level V: 1000 mg/m\^2 GEM / 9.0 mg/m\^2 PM060184 | 5 |
| GEM/PM060184 Dose Level VI Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level VI: 1000 mg/m\^2 GEM / 9.3 mg/m\^2 PM060184 | 9 |
| GEM/PM060184 Dose Level VII Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level VII:1000 mg/m\^2 GEM / 10.0 mg/m\^2 PM060184 | 16 |
| GEM/PM060184 Dose Level VIII Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk.
Administration of study treatment was as follows:
* GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by:
* PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device.
Dose Level VIII:1000 mg/m\^2 GEM / 10.5 mg/m\^2 PM060184 | 6 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Dose Level I | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level I | Never Treated | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level I | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level I | Progressive disease | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level I | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level II | Non-treatment-related AE | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level II | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level II | Progressive disease | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level II | Treatment-related AE | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level II | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level III | Progressive disease | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Dose Level III | Treatment-related AE | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Dose Level III | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Dose Level IV | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Level IV | Progressive disease | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 |
| Dose Level IV | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Level V | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Level V | Progressive disease | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 |
| Dose Level V | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Level VI | Progressive disease | 0 | 0 | 0 | 0 | 0 | 7 | 0 | 0 |
| Dose Level VI | Treatment-related AE | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dose Level VI | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dose Level VII | Death | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Dose Level VII | Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 10 | 0 |
| Dose Level VII | Treatment-related AE | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Dose Level VII | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Dose Level VIII | Never treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Level VIII | Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Dose Level VIII | Treatment-related AE | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Level VIII | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.0 years | 58.5 years | 65.0 years | 68.0 years | 56.0 years | 62.0 years | 67.0 years | 59.0 years | 49.0 years |
| Age, Customized 18-55 | 19 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 5 Participants |
| Age, Customized 56-75 | 35 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 5 Participants | 11 Participants | 1 Participants |
| Age, Customized >75 | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Agents of prior anticancer therapies | 4 Agents | 4.5 Agents | 5 Agents | 3 Agents | 4 Agents | 3 Agents | 4 Agents | 4.5 Agents | 5 Agents |
| Body surface area | 1.8 m^2 | 2.0 m^2 | 1.7 m^2 | 1.9 m^2 | 1.6 m^2 | 1.8 m^2 | 1.7 m^2 | 1.8 m^2 | 1.6 m^2 |
| Bulky disease | 14 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 2 Participants |
| ECOG PS 0 | 15 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 3 Participants |
| ECOG PS 1 | 42 Participants | 4 Participants | 5 Participants | 2 Participants | 4 Participants | 7 Participants | 6 Participants | 11 Participants | 3 Participants |
| Lines of prior anticancer therapies | 3 lines | 3 lines | 2 lines | 3 lines | 2 lines | 3 lines | 3 lines | 3 lines | 3.5 lines |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 16 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Not provided/not available | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 5 Participants | 2 Participants |
| Region of Enrollment Spain | 21 participants | 1 participants | 1 participants | 2 participants | 4 participants | 4 participants | 3 participants | 4 participants | 2 participants |
| Region of Enrollment United States | 36 participants | 3 participants | 4 participants | 3 participants | 1 participants | 5 participants | 4 participants | 12 participants | 4 participants |
| Sex: Female, Male Female | 42 Participants | 2 Participants | 5 Participants | 4 Participants | 1 Participants | 6 Participants | 4 Participants | 15 Participants | 5 Participants |
| Sex: Female, Male Male | 15 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants |
| Site involvement at baseline | 4 sites | 4.5 sites | 3 sites | 3 sites | 3 sites | 4 sites | 4 sites | 4 sites | 3.5 sites |
| Time from diagnosis to first infusion | 48.8 months | 23.2 months | 34.3 months | 23.4 months | 30.2 months | 33.9 months | 43.0 months | 44.5 months | 48.8 months |
| Time from last progressive disease to first infusion | 1.4 months | 2.2 months | 1.7 months | 1.4 months | 1.6 months | 2.4 months | 1.0 months | 1.2 months | 0.7 months |
| Time-to-progression of last prior therapy | 3.7 months | 3.4 months | 6.7 months | 11.7 months | 1.6 months | 5.4 months | 3.8 months | 3.0 months | 2.9 months |
| Tumor type Adenocarcinoma or carcinoma of unknown primary site | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumor type Breast cancer | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Tumor type Epithelial ovarian cancer | 13 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 1 Participants |
| Tumor type GCTs | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Tumor type GIST | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Tumor type Gynecological (endometrial or cervical) | 13 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 6 Participants | 1 Participants |
| Tumor type Head and neck cancer | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Tumor type NSCLC | 18 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 0 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 1 / 7 | 0 / 4 | 0 / 5 | 1 / 5 | 0 / 9 | 5 / 16 | 0 / 5 |
| other Total, other adverse events | 4 / 4 | 7 / 7 | 4 / 4 | 5 / 5 | 5 / 5 | 9 / 9 | 16 / 16 | 5 / 5 |
| serious Total, serious adverse events | 2 / 4 | 3 / 7 | 2 / 4 | 1 / 5 | 3 / 5 | 3 / 9 | 8 / 16 | 4 / 5 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities
Dose-limiting toxicities were defined as: * Grade 4 neutropenia lasting \>3 days * Grade≥3 febrile neutropenia of any duration or neutropenic sepsis * Grade 4 thrombocytopenia or grade 3 with any major bleeding episode requiring a platelet transfusion * Grade 4 ALT/AST increase, or grade 3 lasting \>7 days * Treatment-related grade≥2 ALT/AST increase concomitantly with ≥2 x ULN total bilirubin increase and normal AP * Any other grade≥3 non-hematological AE that was suspected to be related to study drugs, except nausea/vomiting, hypersensitivity reactions, extravasations, grade 3 asthenia lasting less than one week, anorexia, and non-clinically relevant isolated biochemical abnormalities * Delay in the administration of Cycle 2 of the combination exceeding seven (+1) days of the treatment due date due to any AEs related to study drugs. * The following circumstances were to be discussed between the Principal Investigator and the Sponsor, and the final consensus had to be documented
Time frame: From the start of treatment to the end of cycle one which are 3 weeks
Population: Thirteen patients were not evaluable: 11 patients because they did not complete Cycle 1, and two patients because they were withdrawn from the study before receiving the first study drug infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEM/PM060184 Dose Level I | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| GEM/PM060184 Dose Level II | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| GEM/PM060184 Dose Level III | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| GEM/PM060184 Dose Level IV | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| GEM/PM060184 Dose Level V | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| GEM/PM060184 Dose Level VI | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| GEM/PM060184 Dose Level VII | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| GEM/PM060184 Dose Level VIII | Number of Participants With Dose Limiting Toxicities | 1 Participants |
Secondary
Number of Participants With Clinical Benefit
Clinical benefit defined as any response or stable disease ≥4 months. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Every two cycles (every six weeks ± one week) until Cycle 4, and then every three cycles (every nine weeks ± one week) while on treatment, up to 2 years
Population: Eleven patients were not evaluable: nine patients because they were withdrawn from the study before undergoing a tumor assessment, and two patients because they were withdrawn from the study before receiving the first study drug infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEM/PM060184 Dose Level I | Number of Participants With Clinical Benefit | 1 Participants |
| GEM/PM060184 Dose Level II | Number of Participants With Clinical Benefit | 3 Participants |
| GEM/PM060184 Dose Level III | Number of Participants With Clinical Benefit | 2 Participants |
| GEM/PM060184 Dose Level IV | Number of Participants With Clinical Benefit | 1 Participants |
| GEM/PM060184 Dose Level V | Number of Participants With Clinical Benefit | 1 Participants |
| GEM/PM060184 Dose Level VI | Number of Participants With Clinical Benefit | 2 Participants |
| GEM/PM060184 Dose Level VII | Number of Participants With Clinical Benefit | 6 Participants |
| GEM/PM060184 Dose Level VIII | Number of Participants With Clinical Benefit | 2 Participants |