Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Neoadjuvant: Prior to surgery, participants receive up to 3 cycles (cycle length: 3 weeks) of sintilimab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with neoadjuvant chemotherapy, consisting of albumin-bound paclitaxel \[260 mg/m\^2, IV; given on cycle day 1\] and carboplatin \[AUC 5- 6mg/mL/min, IV; given on cycle day 1 \] .

Adjuvant: Followed by surgery within the 3-5th week after the last dose of sintilimab, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient. The maintenance treatment of sintilimab \[200 mg, intravenous (IV); given on cycle day 1; cycle length: 3 weeks\] may be selected upon subject request for up to 1 year.

Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of sintilimab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with neoadjuvant chemotherapy, consisting of albumin-bound paclitaxel \[260 mg/m\^2, IV; given on cycle day 1\] and carboplatin \[AUC 5- 6mg/mL/min, IV; given on cycle day 1 \] .

Adjuvant: Followed by surgery within the 3-5th week after the last dose of sintilimab, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient. The maintenance treatment of sintilimab \[200 mg, intravenous (IV); given on cycle day 1; cycle length: 3 weeks\] may be selected upon subject request for up to 1 year.

200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.

Sintilimab

AUC 5-6 mg/mL/min by IV infusion Q3W, given on cycle day 1.

260 mg/m\^2 by IV infusion Q3W, given on cycle day 1.

Fuming Qiu

Fuming Qiu, PhD

Junqiang Fan, PhD

This is a Phase 3, prospective, randomized, open-label, multi-center study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for Resectable Squamous Cell NSCLC. This trial will also explore the biomarkers of neoadjuvant immunochemotherapy.

This is a Phase 3, prospective, randomized, open-label, multi-center study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for Resectable Squamous Cell NSCLC. In this trial, eligible subjects will be randomly assigned to arm A and arm B (1:1). Subjects in arm A will receive 3 cycles of neoadjuvant sintilimab with chemotherapy and arm B will receive 4 cycles of neoadjuvant sintilimab with chemotherapy, followed by surgery within the 3-5th week after the last dose of sintilimab. After operation, both subjects in arm A and B can receive the treatment of sintilimab for up to 1 year according to the requirements of patients. The primary purpose is MPR rate of Resectable Squamous Cell NSCLC with different cycles of sintilimab combined with chemotherapy, which is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.

Neoadjuvant Therapy of Sintilimab Combined With Chemotherapy for Resectable Squamous Cell NSCLC（neoSCORE Ⅱ）

Neoadjuvant Therapy of Sintilimab Combined With Chemotherapy for Resectable Squamous Cell NSCLC（neoSCORE Ⅱ）：A Prospective, Randomized, Open-Label, Multi-Center Phase 3 Trial

MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.

pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens.

ORR is defined as the percentage of participants having a complete response or a partial response, measured by RECIST 1.1.

2 years DFS rate is defined as the percentage of participants having no recurrence, distant metastasis or death within 2 years after operation.

2 years OS rate is defined as the percentage of participants having no death of any cause within 2 years after operation.The Kaplan-Meier estimator will be used to estimate median OS and its 95%CI and the survival curve.

2 years EFS rate is defined as the percentage of participants having no radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause within 2 years after randomization.

Second Affiliated Hospital, School of Medicine, Zhejiang University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma, Neuroendocrine

Sarcoma

Carcinoma, Renal Cell

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Renal Cell Carcinoma

Soft Tissue Sarcoma

Lymphosarcoma

Clear Cell Renal Cell Carcinoma

Part 1 - Dose escalation of DS-3078a to determine the maximum tolerated dose (MTD) will be guided by the modified continuous reassessment method (mCRM) using a Bayesian logistic regression model (BLRM) following escalation with overdose control (EWOC) principle.

Before starting mCRM, initial dose escalation will proceed following an accelerated titration in which single subjects will be enrolled into sequential dose levels with a dose increment of up to 100% from the previous dose.

Upon completion of Part 1 with established MTD and tentative recommended phase 2 dose (RP2D), the Dose Expansion (Part 2) will begin with the intention of further assessing the safety and tolerability of DS-3078a, confirming the RP2D, determining the Pharmacodynamic response in tumor samples, and evaluating preliminary efficacy of DS-3078a in subjects.

DS-3078a will be administered as oral capsules once daily and will be supplied in 5, 20, 50, and 150 mg capsules.

DS-3078a

DS-3078a will be evaluated as a single agent in subjects with advanced solid tumor malignancies or lymphomas refractory to standard treatment or for which no standard treatment is available.

This is a Phase 1, open-label study of DS-3078a to assess safety and tolerability, identify the maximum tolerated dose (MTD) and tentative recommended phase 2 dose (RP2D), and assess pharmacokinetic and pharmacodynamic properties in subjects with advanced solid tumor malignancies or lymphomas. The study will include 2 parts: Dose Escalation and Dose Expansion.

A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

A Phase 1, Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

To determine the maximum tolerated dose (MTD) and tentative recommended Phase 2 dose (RP2D) of DS 3078a

determine the Cmax (maximum concentration) of DS-3078a administered under fed and unfed conditions

determine the effect of DS-3078a on glucose metabolism by measuring serum glucose and C peptide

assess the pharmacodynamic effects of DS 3078a by determining tumor glucose uptake using (18F) fluorodeoxyglucose positron emission tomography (FDG-PET)

assess tumor response to DS-3078a in subjects with advanced non-Hodgkin lymphomas or advanced solid tumor types in which the mammalian target of rapamycin (mTOR) signaling pathway is frequently activated

assess the pharmacodynamic effects of DS 3078a by measuring v-akt murine thymoma viral oncogene homolog 1 (Akt) phosphorylation in platelet rich plasma (PRP)

determine the Area under the concentration versus time curve (AUC) of DS-3078a administered under fed and unfed conditions

determine the time of maximum concentyration (Tmax) of DS-3078a administered under fed and unfed conditions

determine the terminal half-life (T1/2) of DS-3078a administered under fed and unfed conditions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Therapy of Sintilimab Combined With Chemotherapy for Resectable Squamous Cell NSCLC（neoSCORE Ⅱ）	NCT05429463	Squamous Cell N...	Sintilimab Carboplatin Albumin-Bound P...	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas	NCT01588678	Advanced Solid ... Lymphoma	DS-3078a	18 Years -	Daiichi Sankyo
Neoadjuvant Therapy of Sintilimab Combined With Chemotherapy for Resectable Squamous Cell NSCLC（neoSCORE Ⅱ）	NCT05429463	Squamous Cell N...	Sintilimab Carboplatin Albumin-Bound P...	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University

Spots Global Cancer Trial Database for squamous cell nsclc