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(12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE

This article reviews clinical trials investigating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE, also known as daraxonrasib or RMC-6236. Trials are evaluating this treatment in patients with RAS-mutated cancers, particularly non-small cell lung cancer and pancreatic cancer.

Table of Contents

Overview of Clinical Research

Clinical trials are currently investigating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE, also known as daraxonrasib or RMC-6236, as a potential treatment for cancers with specific genetic mutations[1][2][1][3]. This investigational substance is being evaluated across multiple phases of clinical research, from early safety studies to large comparative trials against standard treatments.

The research program includes five major clinical trials with a total planned enrollment of over 1,700 patients[1][2][1][3]. These trials are designed to evaluate the substance both as a single agent and in combination with other anticancer therapies. All trials have been authorized and are focusing on patients whose tumors carry mutations in the RAS gene, which is one of the most commonly mutated genes in human cancers.

Understanding the Investigational Substance

The substance (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE is referred to by its development code RMC-6236 and the generic name daraxonrasib in clinical trial documentation[1][2][1][3]. This investigational drug is being studied specifically for cancers that have mutations in the RAS gene family.

RAS mutations are genetic changes that cause cells to grow and divide uncontrollably. These mutations are found in approximately 30% of all human cancers and have historically been very difficult to target with medications. The specific mutations being studied in these trials include G12D, G12C, and other G12 variants, which refer to changes at position 12 of the RAS protein[1][2][1][3].

Target Patient Populations and Cancer Types

The clinical trials investigating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE are focused on two primary cancer types:

  • Non-small cell lung cancer (NSCLC): The majority of trials are enrolling patients with advanced NSCLC that carries RAS mutations. This includes patients with G12D mutations, G12C mutations, and other RAS mutations[1][1][3].
  • Metastatic pancreatic ductal adenocarcinoma (PDAC): One large Phase 3 trial is specifically studying patients with pancreatic cancer that has spread to other parts of the body[2].

Most trials require that patients have advanced or metastatic cancer, meaning the disease has spread beyond its original location. Many studies specifically enroll patients who have received previous treatments that did not work or stopped working[2][3]. The pancreatic cancer trial, for example, focuses on patients with previously treated metastatic disease[2].

Some trials also include patients with other types of RAS-mutated solid tumors, allowing researchers to evaluate the substance in a broader range of cancers beyond lung and pancreatic cancer[1][1].

Phase 1 Clinical Trials

Two Phase 1 trials are evaluating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in combination with other treatments. Phase 1 trials are the earliest stage of testing in humans and focus primarily on safety and determining the appropriate dose.

Subprotocol A: RAS G12C-Mutated NSCLC

This trial (NCT06162221, Subprotocol A) is enrolling 267 patients with RAS G12C-mutated solid tumors, with a focus on NSCLC[1]. The primary objectives are to evaluate the safety and tolerability of RMC-6291 (another investigational drug) in combination with pembrolizumab, with or without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE, and with or without chemotherapy[1].

A key goal of this study is to define the recommended Phase 2 dose schedule (RP2DS) for RMC-6291 in these combinations specifically for patients with RAS G12C-mutated NSCLC[1]. The RP2DS is the dose and schedule that will be used in later-stage trials based on the balance of effectiveness and side effects observed in Phase 1.

Subprotocol B: RAS-Mutated NSCLC

The second Phase 1 trial (NCT06162221, Subprotocol B) is larger, planning to enroll 356 patients with RAS-mutated NSCLC[1]. This study evaluates (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in combination with pembrolizumab, with or without chemotherapy[1].

The objective is to evaluate the safety and tolerability of these combinations in patients with advanced RAS-mutated NSCLC[1]. Unlike Subprotocol A, which focuses on the specific G12C mutation, this trial includes patients with various RAS mutations, providing broader information about the substance’s safety profile.

Phase 2 Clinical Trials

One Phase 2 trial is investigating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in patients with RAS G12D-mutated NSCLC. Phase 2 trials continue to evaluate safety but place more emphasis on whether the treatment shows signs of working against cancer.

RAS G12D-Mutated NSCLC Study

This trial (NCT06162221) plans to enroll 216 patients with RAS G12D-mutated NSCLC[1]. The study is evaluating zoldonrasib (RMC-9805) with or without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in combination with pembrolizumab, with or without chemotherapy[1].

The primary objectives are to evaluate the safety and tolerability of these combinations and to determine the RP2DS for RMC-9805 with or without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in combination with pembrolizumab in this specific patient population[1]. This trial is particularly important because it focuses on the G12D mutation, which is one of the most common RAS mutations in lung cancer.

Phase 3 Clinical Trials

Two large Phase 3 trials are comparing (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE against standard treatments. Phase 3 trials are the final stage before a drug can be approved for use and are designed to definitively show whether the new treatment is better than existing options.

Metastatic Pancreatic Cancer Trial

The largest trial (2024-516063-89-00) is enrolling 460 patients with previously treated metastatic pancreatic ductal adenocarcinoma[2]. This study compares (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE versus the investigator’s choice of standard therapy in patients with RAS G12 mutations[2].

The trial includes multiple standard treatment options as comparators, including:

  • Gemcitabine hydrochloride combined with paclitaxel albumin-bound
  • FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan, and oxaliplatin)
  • Gemcitabine with various other chemotherapy agents[2]

The primary objective is to compare the effect of treatment with (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE versus standard therapy on progression-free survival (PFS) and overall survival (OS) in the RAS G12 population[2].

RAS-Mutated NSCLC Trial

The second Phase 3 trial (NCT06881784) is enrolling 420 patients with RAS-mutated NSCLC[3]. This study compares the treatment effect of (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE (daraxonrasib) versus docetaxel in the RAS (G12X-C) population[3].

Docetaxel is a chemotherapy drug commonly used as a standard treatment for patients with NSCLC whose cancer has progressed after initial therapy. This trial will provide critical information about whether (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE offers advantages over this established treatment option.

Treatment Combinations Being Studied

Most clinical trials are investigating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in combination with other anticancer treatments rather than as a single agent. This approach is common in modern cancer research, as combining drugs with different mechanisms of action may provide better results than single treatments.

Combination with Immunotherapy

Several trials are combining (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE with pembrolizumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells[1][1]. Pembrolizumab is already approved for treating various types of cancer and works by blocking a protein called PD-1 that prevents immune cells from attacking tumors.

The rationale for this combination is that targeting RAS mutations with (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE while simultaneously activating the immune system with pembrolizumab may provide complementary anticancer effects.

Combination with Chemotherapy

Some trials are adding chemotherapy to the combination of (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE and pembrolizumab[1][1]. Chemotherapy uses drugs that kill rapidly dividing cells, including cancer cells. The Phase 1 and Phase 2 trials include treatment arms that evaluate these triple combinations to determine if adding chemotherapy provides additional benefit.

Combination with Other Targeted Therapies

The Phase 2 trial in RAS G12D-mutated NSCLC is investigating the combination of zoldonrasib (RMC-9805) with (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE[1]. Both of these investigational drugs target RAS mutations, and combining them may provide more complete blockade of the RAS signaling pathway that drives cancer growth.

Similarly, one Phase 1 trial is evaluating RMC-6291 with or without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE in patients with RAS G12C-mutated cancers[1]. This allows researchers to compare the effects of each drug alone versus the combination.

Study Endpoints and Measurements

Clinical trials use specific measurements called endpoints to determine whether a treatment is working. Different phases of trials focus on different types of endpoints.

Safety and Tolerability Endpoints

All trials evaluating (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE include safety as a primary or important secondary objective[1][1]. Safety endpoints measure what side effects occur, how severe they are, and how often they happen. This information helps researchers understand the risks of the treatment and determine the appropriate dose.

The Phase 1 and Phase 2 trials specifically aim to determine the RP2DS, which is the dose and schedule that balances effectiveness with acceptable side effects[1]. This dose will then be used in larger Phase 3 trials.

Progression-Free Survival

Progression-free survival (PFS) is a primary endpoint in the Phase 3 pancreatic cancer trial[2]. PFS is defined as the time from randomization (when patients are assigned to a treatment group) until disease progression or death from any cause, whichever occurs first[2].

Disease progression is measured using RECIST v1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1), which is a standardized way to measure tumor size using imaging scans like CT or MRI[2]. The measurements are made by a blinded independent central review (BICR), meaning experts who don’t know which treatment patients received evaluate the scans to ensure unbiased assessment[2].

Overall Survival

Overall survival (OS) is another primary endpoint in the Phase 3 pancreatic cancer trial[2]. OS is defined as the time from randomization until death from any cause[2]. Overall survival is considered the most important measure of treatment benefit because it directly measures how long patients live, regardless of whether their cancer progresses.

Both PFS and OS are critical for understanding whether (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE provides meaningful clinical benefit compared to standard treatments in patients with RAS-mutated cancers.

Trial ID Phase Condition Studied Status Enrollment Key Combinations
NCT06162221 (Sub A) Phase 1 RAS G12C-mutated NSCLC Authorised 267 RMC-6291 with pembrolizumab, with/without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE
NCT06162221 (Sub B) Phase 1 RAS-mutated NSCLC Authorised 356 (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE with pembrolizumab, with/without chemotherapy
NCT06162221 Phase 2 RAS G12D-mutated NSCLC Authorised 216 RMC-9805 with/without (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE with pembrolizumab
2024-516063-89-00 Phase 3 Metastatic pancreatic ductal adenocarcinoma Authorised 460 (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE vs standard therapy
NCT06881784 Phase 3 RAS-mutated NSCLC Authorised 420 (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE vs docetaxel

FAQ

  • What types of cancer are being studied in trials with (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE? Clinical trials are investigating this substance primarily in patients with non-small cell lung cancer and metastatic pancreatic ductal adenocarcinoma. These trials specifically focus on patients whose tumors have RAS mutations, particularly G12D, G12C, and other G12 variants.
  • What phases of clinical trials are currently studying (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE? The substance is being studied in Phase 1, Phase 2, and Phase 3 clinical trials. Phase 1 and 2 trials focus on evaluating safety, tolerability, and determining recommended doses, while Phase 3 trials compare the treatment against standard therapies.
  • Is (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE being studied alone or with other treatments? Most trials are studying this substance in combination with other anticancer treatments. Common combinations include pembrolizumab (an immunotherapy), chemotherapy drugs like gemcitabine and paclitaxel, and another investigational drug called zoldonrasib (RMC-9805).
  • Who can participate in these clinical trials? Trials are enrolling patients with advanced or metastatic RAS-mutated cancers, specifically those with G12D, G12C, or other G12 mutations. Participants typically have non-small cell lung cancer or pancreatic ductal adenocarcinoma that has progressed after previous treatments.
  • What are the main goals of these clinical trials? The primary goals include evaluating the safety and tolerability of the treatment, determining the recommended dose for future studies, and comparing treatment effectiveness against standard therapies. Trials measure outcomes like progression-free survival and overall survival.

Ongoing Clinical Trials on (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE

  • Study of zoldonrasib with daraxonrasib, pembrolizumab and chemotherapy in patients with RAS G12D-mutant non-small cell lung cancer

    Recruiting

    1 1 1
    Investigated drugs:
    Austria Czechia Denmark France Germany Greece +3

  • Study comparing RMC-6236 and docetaxel in previously treated patients with advanced or metastatic non-small cell lung cancer who have RAS mutations

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium France Germany Ireland Italy The Netherlands +2

  • Study of RMC-6291 and Pembrolizumab with or without Chemotherapy for Patients with Advanced KRAS G12C Mutated Lung Cancer

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy The Netherlands Spain

  • Study of RMC-6236 and Pembrolizumab with or without Chemotherapy for Patients with RAS-Mutated Non-Small Cell Lung Cancer

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy The Netherlands Spain

  • A study of daraxonrasib (RMC-6236) compared to observation in patients with resected pancreatic cancer following chemotherapy

    Not yet recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy Spain

  • Study of RMC-6236 compared to standard therapy in previously treated metastatic pancreatic ductal adenocarcinoma

    Not recruiting

    1 1 1 1
    Investigated drugs:
    France Germany Italy Spain

Glossary

  • RAS mutation: A change in the RAS gene that causes cells to grow uncontrollably, leading to cancer. RAS mutations are found in many types of cancer and make tumors difficult to treat.
  • G12D, G12C mutations: Specific types of RAS gene mutations where the amino acid at position 12 is changed. G12D and G12C are among the most common RAS mutations in cancer.
  • Non-small cell lung cancer (NSCLC): The most common type of lung cancer, accounting for about 85% of all lung cancers. It grows more slowly than small cell lung cancer.
  • Pancreatic ductal adenocarcinoma (PDAC): The most common type of pancreatic cancer that starts in the ducts of the pancreas. It is often diagnosed at advanced stages and is difficult to treat.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives with cancer without it getting worse. It is a common measure of treatment effectiveness.
  • Overall survival (OS): The length of time from the start of treatment that patients are still alive. It is considered the most important measure of treatment benefit.
  • Pembrolizumab: An immunotherapy drug that helps the immune system recognize and attack cancer cells. It is approved for treating various types of cancer.
  • RP2DS: Recommended Phase 2 Dose Schedule – the dose and schedule of a drug that will be used in further clinical trials based on safety and effectiveness data.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors – a standardized way to measure whether cancer tumors are shrinking, staying the same, or growing during treatment.
  • Metastatic cancer: Cancer that has spread from where it started to other parts of the body. Metastatic cancer is more difficult to treat than cancer that has not spread.
  • BICR: Blinded Independent Central Review – an independent evaluation of imaging scans by experts who do not know which treatment patients received, ensuring unbiased assessment.
  • Chemotherapy: Treatment that uses drugs to kill cancer cells or stop them from growing. It can be given alone or combined with other cancer treatments.

References