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Bronchial Neoplasms

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Small Cell Lung Cancer

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Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Patients will receive atezolizumab at a fixed dose of 1200 mg intravenously (i.v.) as a 60-minute infusion (the second and subsequent infusions may be administered over 30 minutes) followed by PM01183 at a starting dose of 2.5 mg/m2 i.v. as a 1-hour infusion on Day 1 every three weeks (q3wk). Following analysis of cohorts, dose levels can be escalated from 2.5mg to 3.2, to a maximum dose of 3.5 mg of PM01183

PM 01183

Luis Paz Ares, MD PhD

Reyes Bernabé

Laura Medina

Marta López- Brea

Alejandro Navarro

Mª Rosario García

Laura Mezquita

Margarita Majem

Santiago Ponce

Javier de Castro

Maria Eugenia Olmedo

Silverio Ros

David Vicente

Dolores Isla

Santiago Ponce, MD

Prospective, open-label, uncontrolled and multicenter phase I-II study in SCLC patients with ECOG PS 0-1 who have failed one prior platinum-containing line but no more than one chemotherapy-containing line. The study will be divided into two parts: a dose-ranging phase I with escalating doses of PM01183 in combination with a fixed dose of atezolizumab, followed by a single-arm phase II part with expansion at the RD determined during the phase I.

Phase I Patients will receive atezolizumab at a fixed dose of 1200 mg intravenously (i.v.) followed by PM01183 at a starting dose of 2.5 mg/m2 i.v. as a 1-hour infusion on Day 1 every three weeks (q3wk). PM01183 doses will be escalated in successive cohorts of patients following a modified Fibonacci scheme and a classical 3+3 design, and according to observed tolerance and safety.

Phase II Patients will receive atezolizumab i.v. as a 60-minute infusion (the second and subsequent infusions may be administered over 30 minutes) followed by PM01183 i.v. as a 1-hour infusion on Day 1 q3wk, at the RD determined during the phase I part.

It is expected that approximately 50% of patients included were previously treated with chemotherapy and the other 50% with immunotherapy and chemotherapy. In case one of the groups reaches 50% of the total number of patients expected to be recruited, no further patient will be included in this group and accrual will be limited to patients with the other group.

It is expected that approximately 50% of the patients included in the phase II part will be platinum-resistant \[i.e., chemotherapy-free interval (CTFI) 30 to \< 90 days from the end of first-line platinum-based chemotherapy\] and 50% will be platinum-sensitive (i.e., CTFI ≥ 90 days), so as to assess efficacy in both settings. However in case that one of the CTFI groups reaches 60% of the total number of patients expected to be recruited, no further patient will be included in this group and accrual will be limited to patients with the other CTFI group.

Prospective, open-label, uncontrolled and multicenter phase I-II study

Study to Assess Safety,Tolerability,Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer.

Phase I-II Study to Assess the Safety, Tolerability and Efficacy of PM01183 and Atezolizumab in Patients With Advanced Small Cell Lung Cancer That Progressed Following Prior Therapy With Platinum-Based Chemotherapy.

The MTD will be the lowest dose level explored during dose escalation at which more than one third of evaluable patients experience a DLT during Cycle 1.

The RD will be the highest dose level explored during dose escalation at which less than one third of evaluable patients experience a DLT during Cycle 1.

the time from the date of registration to the date of documented progression per RECIST v.1.1 or death. If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

Duration of response will be calculated from the date of first documentation of response per RECIST v.1.1 (complete or partial response, whichever comes first) to the date of documented PD or death. The censoring rules defined above for PFS will be used for DoR.

defined as percentage of evaluable patient with complete response, partial response or stable disease lasting ≥3 months, as defined by RECIST v1.1.

calculated from the date of registration to the date of death (death event) or last contact (in this case, survival will be censored on that date).

will be the Kaplan-Meier estimates of the probability of being alive at these time points

PK parameters will be evaluated in plasma by standard non-compartmental methods (compartmental modeling may be performed if appropriate).The dose-exposure relationships for maximum plasma concentration (Cmax) and any potential PK interaction of atezolizumab over PM01183 will be explored.

In order to explore factors that may help explain individual variability in the main PK parameters, the presence or absence of germline mutations or polymorphisms in genes that may be involved in the metabolism and/or transport of PM01183 will be analyzed in leukocyte DNA extracted from one blood sample (10 mL) obtained at any time during the study, but preferably just before treatment start in Cycle 1 along with the first PK sample

In order to determine predictive/prognostic markers of response and/or resistance to PM01183 and atezolizumab, tumor samples available at baseline and blood samples (Day 1 of every cycle and end-of-treatment) wil be evaluated in all patients. In addition, on- treatment tumor samples from biopsy (4ht to 6ht weeks after treatment onset) wil be obtained and evaluated for patients cosenting to PGx sub- study.

For tumor biomarkers research, tumor samples will be collected on-treatment to be analyzed at the end of the study. The on-treatment biopsy will be optional, requiring specific patient consent.

The on-treatment tumor samples will be compared to baseline tumor samples and the biomarker to analize are:

PD-L1 and PD-L2 expression in tumor cells and in tumor-infiltrating immune cells, presence of CD8+ T cell and CD4+ T cell in stromal-tumor edge and inside the tumor parenchyma, tumor-infiltrating lymphocyte (TIL) density, expression of granzyme B, the activated transcription factor signal transducer and activator of transcription 1 (pSTAT1), Ki67, interferon gamma (IFNƔ), tumor necrosis factor alpha (TNF-α), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), fractalkine, lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin protein 3 (TIM-3) by IHC;

and Tumor mutational burden by DNAseq with Foundation One (or another similar validated panel).

PK parameters will be evaluated in plasma by standard non-compartmental methods (compartmental modeling may be performed if appropriate).The area under the curve (AUC) will be evaluated, and any potential PK interaction of atezolizumab over PM01183 will be explored.

For those patients specifically consenting, blood samples for the evaluation of biomarkers will be drawn just before treatment on Day 1 of each cycle and at EOT.

The biomarker to analize are:

• Plasma cytokine analysis by enzyme-linked immunosorbent assay (ELISA): IFNƔ, TNF-α, interleukins IL-1β, IL-6 and IL-18, and CXCL11 (ITAC).

Spots Global Cancer Trial Database for pm 01183

Every month we try and update this database with for pm 01183 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pm 01183

Every month we try and update this database with for pm 01183 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pm 01183 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.